CN101578065A - Method of utilising measurements of threshold of pain - Google Patents
Method of utilising measurements of threshold of pain Download PDFInfo
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Abstract
A method of determining the sympathetic tone and/or level of stress and/or level or warning system sensitivity includes the steps of: measuring an applied stimulation at a threshold value of the stimulation in one or more sympathetic tone-neutral points and measuring an applied stimulation at the same threshold value in one or more sympathetic tone-dependent points. The invention further relates to a system for applying and measuring a stimulation, and the use of a system for applying and measuring a stimulation for determining the sympathetic tone including the steps of: measuring an applied stimulation at a threshold value of the stimulation at one or more sympathetic tone-neutral points and measuring an applied stimulation at the same threshold value of the stimulation at one or more sympathetic tone-dependent points.
Description
Technical field
The present invention relates to the method for measuring at once of sympathetic tone/WSS/DRS and be used for the system of its measurement.Since this method for the individual provide may with the mensuration at once of the sympathetic tone of the track record combination of measuring, it is suitable for measuring healthy individual on health and the probability of putting up the best performance mentally.The present invention relates to the purposes that system of the present invention is used to measure sympathetic tone in addition, and the nociception measurement is used to measure the purposes of sympathetic tone.
Background technology
In mammal, nervous system is divided into somatic nervous system and autonomic nervous system with regard to its function.Autonomic nervous system is automatically carried out function with reflexive ground.Autonomic nervous system can further be divided into the sympathetic nerve and the parasympathetic nervous system of counterproductive.Sympathetic nerve and parasympathetic nervous have opposite effect.
Sympathetic nervous system makes and can handle urgent dangerous situation/attack in the mode of the best with the resource of so-called " stress " transfer organism.When stress caused essential change of body function, health was set up a kind of new state, is called as " stress stage ".In this stage, the people thinks deeply faster and more clear on intelligence, can be primarily focused in its thinking simultaneously.In order to support this purpose, stoped incoherent sensory impression effectively.On the health, health is by shortening the response time, increase muscle strength, making the coordination between oxyesthesia and optimization thinking and the motor skill be used as response.
In a word, the above qualification " stress stage " is positive physiological phenomenon, and it reveals to come with the scale that is fit to, and carries out suitable balance with necessary recovery, and described recovery is worked when parasympathetic nervous system is preponderated, as described below.
Parasympathetic nervous system is regulated biological process, thus described course recovery and increase the resource of organism and guarantee acute/instantaneous stress situation in have the essential resource that can transfer to use.
On the physiology, the secretions that increases in pulse and blood pressure and the inhibition body of gland via orthosympathetic simulation forms, or the like.And parasympathetic nervous especially is reduced to the level of physiology's rest state with heart rate and blood pressure, and stimulates glandular secretion.In stress process, the sympathetic nervous system activation.
Stress be pleasant, but also can be irritating and be life-threatening sometimes.Be necessary stress two kinds of forms between distinguish: instantaneous with persistent.Instantaneous stress (=acute stress) be prepared physiological status when discovering dangerous sign, that is, and and by nerve centre/hormone signal automatic state that causes in health from brain.Therefore, it plays the effect of self-defense mechanism.Stress level depends on that individuality is to the expection of the consequence of stimulation and the balance between the available resource.When the sign of attack/danger finished, homoiostasis rebulid.If the individual has essential resource to use, then can be with the cognitive situation of positive mode.If situation is represented wherein strain (strain) and surpasses the state of resources of health that then situation is probably by negatively cognitive.If this latter event continues, then the resource of organism may be consumed, and the performance of health reduces.This state be called as lastingly stress or chronic stress, be owing to Long contact time instantaneous stress be related nerve centre process/hormone and during recover insufficient dysfunction that causes the nerve centre/hormone process of brain.It can injure our health.
In its slightest form, the persistent or chronic physical symptom that stress show as appropriateness, for example muscular tone, fatigue or headache.The order of severity more stress the time, experience other symptom, for example for memory problems, be difficult to concentrate and from the form of the misery (for example, cardiopalmus, stomachache, libido reduce) of internal organs.At more serious stress state, social competence also weakens to some extent, for example patience reduction, dysphoria and uncontrolled flying into a rage.In the later case, undressed chronic stress can cause disease, thus disablement after a time.
Health is controlled by the hypothalamic-pituitary-adrenal system the reaction of the perception of above-mentioned strain/danger, and described system activates the release of the steroid hormone (glucocorticoid) that comprises hydrocortisone.In addition, discharge other hormone, especially comprise catecholamines, norepinephrine and the epinephrine of dopamine.As a result, produce one group of physiological reaction, it combines and is called as stress.Basically all systems of health all are affected, and comprise brain, cardiovascular system, immune system, respiratory system and digestive system.
Can past tense in physiology and psychology danger/attack/strain, health loses activity to its reaction and begins convalescent period.
Stress not only by pure physics or the dangerous of pure psychology activate, and activate by our thinking.Many daily living conditions, especially in a hurry, worried, inter personal contact problem and worry economically can not be subjected to activating when life threatens stress the people.But these small daily strained cumulative functions can produce lastingly/chronic stress.
For fear of stress state development and produce negative influence thus, acute or the cumulative stress level of determining the people is absolutely necessary for causing understanding processing and suitable action, its can reduce or eliminate fully cause stress strain and/or increase the individual handle these strained have preparatory, the feasible negative influence that can avoid and/or prevent and stress be relevant is no matter be the individual's or society.Can not will stress itself regard disease as, but cumulatively stress make the individual more responsive, and may develop into disease hitting.
Known many methods are used for determining sympathetic tone (activity of sympathetic nervous system), as measuring of people's stress level, comprise catecholamine (Ekman R. and Lindstedt.G.: " Molekyler in hydrocortisone, the catecholamine (epinephrine and/or norepinephrine) in the measurement serum and hydrocortisone and the measurement urine of measuring in the saliva
Liv og
(molecules in life and death), in Ekman R.and Arnetz B. (red) " Stress; Molekylerne, Individen, Organisationen,
" (stress; Molecules, the individual, organisationand society), Libers publishing firm, Stockholm 2002, pages77-89; Hansen A.M., Garde A.H., Christensen J.M., Eller N.H.﹠amp;
B. " Evaluation of a radioimmunoassay andestablishment of a reference interval for salivary cortisol inhealthy subjects in Denmark ", Scand J Lab Invest 2003; 63:303-10.).Known measurement skin temperature (Normell LA, Wallin BG. " Sympatheticskin nerve activity and skin temperature changes in man " .ActaPhysiol Scand 1974; 91:417-26) and perspire be used to measure stress other known method.
Mensuration stress have many shortcomings with the known method of sympathetic tone, is not that complicated technology analysis, communication and the expense that need relate to delay is exactly that this method can not be accomplished for the impact/influence from physical environment insensitive.For example the determination of serum of hydrocortisone needs lab analysis.In addition, a shortcoming of this mensuration is that the variation of the serum-concentration of hydrocortisone may be that other reason except stress level raises causes.No matter the many shortcomings measured of perspiring are that this assay method may be very insecure, especially therein the hot day how people's stress level is perspired and all increased.
Warning system and defense reaction mechanism are the basic parts of the surviving policy of living organism.The special polymodal receptor of nociceptive system is used to survey histoclastic environmental stimulus, for organism provides unfavorable conditions as the required information of the optimum response-for example reflex response or reaction of retreating.Sensor is for comprising the various external sources that sympathetic nerve imports into and the adjusting sensitivity of endogenous substance, and by the permeable TRPV passage of Ca2+ at the molecular level conditioned reaction.The known pain sensation that stress suppress these sensors usually.
Therefore, the method for need fast, sympathetic tone being measured in reliable and cheap being used to, described sympathetic tone as the people on the health and make the measuring of probability of optimal representation on the intelligence.
Summary of the invention
The inventor found in the past, in important zone, stress increase the pain sensation.Also find defense reaction/reflection by stress being endowed bigger sensitivity, thereby make the existence potentiality improve.
Prove now, in the people observed breastbone stress due to pain sensitivity to increase the retreat corresponding raising of reflecting (NWR) of (with reference to WO 2005/084529 and WO 2006/092146) and the injury of non-understanding relevant, show the possible favourable enhancing of warning system and defense reaction, and the two is related.
Up to now, the local response of tissue injury has been thought in the pain sensitivity increase, as in inflammation, or the general dysfunction in the neurogenic pain; Therefore, it is relevant with defense reaction not know that still pain sensitivity raises.
Sensitivity is measured (as what instructed) by simple and reliable method in this assignee's WO2005/084529 and WO 2006/092146, and shows normalization when the influence of stress-induced finishes.Owing to there is not simple, the objective and reliable method that is used for diagnosing stress at present, can expect that described methodology may be used for practical application widely, be used for wherein professional or layman and may benefit from situation about stress measure reliably, the soldier's that for example is used to fight post-traumatic stress disorder, heart disease, metabolic syndrome (hypertension, hyperliposis, depression and diabetes) and as preventive measure as the part of crowd's health care and the health and happiness that are used for domestic animal.
Therefore, the invention provides the new understanding to the adjusting potentiality of warning system biology and defense reaction, purpose is to improve the existence potentiality, comprises sensory reaction that imports into and the motor reaction that spreads out of.It is emphasized that for observed adjusting to have the basis of known functional, structural and molecule.
At present, the sensitivity of defense reaction increases, and is reflected as the simplest movement response that spreads out of (that is, injury retreat reflection (NWR)), is not suggested the part of the existence potentiality of improving usually when perceiving danger as the animal or human.To by stress or the adjusting of the NWR that causes of other general environmental factors or other defense reaction do not become the problem of research as yet.NWR has been considered to the objective dose dependent response to pain.Yet, in the situation of damage, observe local modulation, protect injured position.
Therefore, the sensitivity and the association between the defense reaction of warning system are new, have represented a new biological study field.
Because brain is in the stimulation that does not have to handle under the situation of conscious perception potentially dangerous, and the conscious perception of clinical symptoms of stress may serious stress situation in be suppressed, discovery of the present invention has been set up a new road in the perception consciously of danger and the research field of the association between the unconscious perception.
At present, identify as yet be used for since stress due to and the physiology method distinguished between active the increasing of sympathetic nervous system due to the physical training.The invention provides this method.
The invention provides the method for measuring sympathetic tone.Described method be fast, simply, reliable and cheap, and can measuring as people's acute and cumulative stress level, but as mentioned above, it can also be used to measure the state of individual warning system sensitivity (WSS) and defense reaction/reflex sensitivity (DRS).
The present invention is provided for implementing the system of described method in addition.
In first aspect, the present invention relates to measure the method for experimenter's sympathetic tone and/or stress level and/or warning system sensitivity state, may further comprise the steps: measure the stimulation that the stimulus threshold with one or more sympathetic tone neutral points applies and measure stimulation with one or more sympathetic tones-same threshold that the subordinate point applies, perhaps measure stimulation that the threshold value with one or more sympathetic tone subordinate points applies and with described threshold value with mensuration or predetermined calibration threshold value compare in advance.In second aspect, the present invention relates to quantitatively and/or qualitative determination comprises people's the WSS/DRS of animal and/or the method for sympathetic tone level and/or stress level, described method comprises:
A) stored calibration threshold value and stimulus threshold, described calibration threshold value is the quantified measures of the sympathetic tone neutral point nociception threshold value on the animal health or in the health, described stimulus threshold is the quantified measures of the nociception threshold value of the sympathetic tone subordinate point in health or on the health, subsequently;
B) by stimulus threshold and calibration threshold value being compared the readout that calculates WSS and/or DRS and/or sympathetic tone and/or stress level, thereby readout is experimenter's WSS/DRS level and/or measuring of stress level and/or sympathetic tone.
Another aspect relates to quantitatively and/or qualitative determination comprises the method for the state of people's the WSS/DRS of animal and/or sympathetic tone and/or stress level, and described method comprises:
A) stored calibration threshold value and stimulus threshold, described calibration threshold value is the quantified measures of the polymorphism receptor cell firing threshold of sympathetic tone neutral point on the animal health or in the health, described stimulus threshold is the quantified measures of the polymorphism receptor cell excitation threshold of sympathetic tone subordinate point on the health or in the health and subsequently;
B) by stimulus threshold and calibration threshold value are compared the readout that calculates warning system sensitivity, the described readout of warning system sensitivity thus, and/or sympathetic tone and/or stress level is the measuring of warning system sensitivity and/or sympathetic tone and/or warning system sensitivity in the animal.
The other aspect of the present invention relates to various actual enforcement of the invention described above method, wherein this enforcement purpose is to optimize treatment and plan, the effectiveness of described treatment and plan and compliance depend on individual subjects to described treatment and plan stress-level and/or sympathetic tone.For example, the present invention relates to be used to control the method for the process of patient treatment scheme, the effectiveness of wherein said scheme and/or patient's compliance depend on described patient's sympathetic tone and/or stress level and/or WSS and/or DRS, and described method comprises
I) in the therapeutic scheme process one or many measure described patient's sympathetic tone and/or stress level and/or WSS and/or DRS state and
Ii) be subjected to adjust described therapeutic scheme from the whole measurement result of the measured value of being benefited of obtaining of described therapeutic scheme and step I based on the patient.
Relevant with these aspects is following method of the present invention, and it is included in thinks by above-mentioned method and to carry out possibility of intervention under the high situation of stress level and/or sympathetic tone and/or WSS and/or DRS level.Or rather, the invention still further relates to be used to prevent undesirable or do not have effect stress method, described method comprises
A) the described herein method that is used for this mensuration by use is measured patient's sympathetic tone and/or stress level and/or WSS and/or DRS level,
And if sympathetic tone and/or stress level and/or the WSS and/or the DRS level of the demonstration of the measured value among step a rising, sympathetic tone subordinate point is stood in a period of time than the more low intensive stimulation of stimulus threshold.
The present invention also comprises disease of patient prognosis assay method, comprises
1) measures patient's sympathetic tone and/or stress level and/or WSS and/or DRS level and subsequently
2) provide the prognosis of disease for the patient by the measurement result in the integrating step 1 in prognosis is measured, compare with the prognosis that shows higher sympathetic tone and/or stress level and/or WSS and/or DRS level in the measurement result of step 1, sympathetic tone that the measurement result demonstration in the step 1 is low and/or stress level and/or WSS and/or DRS level are better prognosis.
The invention still further relates to the stress level evaluation that is used to measure the experimenter whether the method that stress indicate really be provided, comprising based on interview:
A) in interview, by utilize described herein assay method measure patient's sympathetic tone and/or stress level and/or WSS and/or DRS level and
B) determine evaluation based on interview whether provide with step a in the positively related result of measurement result, positive correlation shows that the evaluation based on interview provides real indication.
In the third aspect, the present invention relates to be used to measure the system of sympathetic tone and/or stress level and/or the warning system sensitivity state of the animal that comprises the people, described system comprises:
A) memory device is used for being stored on the human body or nociception calibration threshold value that the sympathetic tone neutral point of human body is measured and be used for being stored on the human body or the nociception stimulus threshold of the sympathetic tone subordinate point mensuration of human body;
B) electronic circuit, it is programmed for and is used for date processing nociception calibration threshold value and nociception stimulus threshold, so that obtain measured value; With
C) be used for the animal health is applied the user's operating equipment that causes uncomfortable stimulation and is suitable for storing user's operation store equipment of operating the nociception stimulus threshold of generation owing to first user;
D) be used for the animal health is applied the user's operating equipment that causes uncomfortable stimulation and is suitable for storing user's operation store equipment of operating the nociception stimulus threshold of generation owing to second user;
Wherein saidly cause that uncomfortable stimulation comprises 1) vibration and/or 2 that applies by first vibration base) heat and/or 3 that applies by first heating base) apply by the first electricity pedestal, and wherein be used to apply the stimulation that the equipment that causes uncomfortable stimulation is suitable for applying to be increased gradually, described memory device is suitable for storing the irritation level in the moment that corresponds respectively to first and second users operation.
Calibration threshold value can be to measure in advance or predetermined value, and it is a permanent storage, for example null value.
In aspect the 6th, the present invention relates to measure nociception and be used for determining experimenter's the WSS and/or the purposes of DRS level.
Assignee's of the present invention pro-International Patent Application WO 2005/084529 and WO2006/092146 disclose system, method and the purposes that is suitable for when realization is of the present invention.Therefore, the present invention includes utilization in WO 2005/084529 and WO 2006/092146 disclosed assay method and system aspect, and to the improvement of disclosed described method, purposes and system among WO 2005/084529 and the WO 2006/092146.Especially, all instructions among WO 2005/084529 and the WO 2006/092146 all are suitable for being used for measuring according to the present invention the WSS level under the situation of in addition necessary variation, and should be appreciated that instruction is used to that to measure the method for sympathetic tone and/or stress level suitable equally when measuring the WSS level according to the present invention in WO 2005/084529 and WO 2006/092146.
Yet, the present invention has also proved to retreat by the injury of measuring animal (comprising the people) reflects WSS and/or the DRS (and stress level)-especially that (NWR) measures animal, according to the present invention, the previous discovery that use is set up the method for measuring stress level and sympathetic tone level at the method and system of WO 2005/084529 and WO 2006/092146 also is proved to be relevant with the threshold value of NWR.
The accompanying drawing summary
Specifically describe the present invention below with reference to accompanying drawing, wherein
Fig. 1 represents the position of the front end sympathetic tone neutral point of clavicle upside, and the position of the sympathetic tone subordinate point Per 1 between nipple and the anterior axillary fold, be the gray shade district, the stain in the gray shade district is represented according to the present invention in Per 1 point of frequent use.
Fig. 2 is illustrated in the position of rear side sympathetic tone neutral point on the spinal column, more properly is at TH 10-11, and between omoplate in the zone corresponding to the position of the rear portion sympathetic tone subordinate point of TH 3-6.
Fig. 3 is illustrated in the position of the front end sympathetic tone neutral point of clavicle upside, with position at the intermediary sympathetic tone subordinate point of breastbone C.V.17, be the gray shade district, the stain in the gray shade district is represented according to the present invention in C.V.17 the point of frequent use.
Fig. 4 represents the position of the front end sympathetic tone neutral point of clavicle upside, and under nipple the position of the sympathetic tone subordinate point St 18 between two ribs, be the gray shade district, the stain in the gray shade district is represented according to the present invention in St 18 point of frequent use.
Fig. 5 represents system of the present invention, and the part of described system is expressed as and is incorporated in the same device.Described device comprises having and is applicable to the pressure base that people's health is applied the contact surface of external pressure, is used to measure the pick off that is applied to the pressure on the health by pressure base.Described device comprises and is used to show the sensing device of reading numerical value.
Fig. 6 represents the end portion of the device of system of the present invention, and described end portion comprises the contact surface that is suitable for the power that applies on people's health and is used to measure the pick off that is applied to the power on the health.
The principle sketch of an embodiment of the system of Fig. 7 presentation graphs 5.
Fig. 8 represents the sketch of stress factor.
Fig. 9 represents to be used for the flow chart of the ultimate principle of date processing.
Figure 10 represents to be used for the profile of mechanical part of actuator of an embodiment of system of the present invention, and described actuator is used for using vibration to carry out mechanical stimulus.
Figure 11 represents the magnetic field by the actuator generation of an embodiment that is used for system of the present invention, and described actuator is used for using vibration to carry out mechanical stimulus.
Figure 12 represents the different piece of the actuator among Figure 10.
Figure 13 represents the principle sketch of the system of Figure 10.
Figure 14 represents the display of actuator control (adjustment of frequency and stroke).
Figure 15 represents the desired temperature as the function of time.
Figure 16 represents the stress factor as the function of time.
Figure 17 represents to be used for the sketch of hardware designs of an embodiment of the system of the present invention of thermostimulation.
Figure 18 represents as the time pulse of the function of time and output pulses Δ t.
Figure 19 represents the result of research that 27 opera singers are carried out, with measured value of the present invention (SA value) as relevant with performance measuring of stress changing.In the research, before song performance, after the process neutralization, carry out the measurement of MBP, PRP, saliva hydrocortisone and SA.The variation of SA value with below be changed significantly relevant, PRP (r=0.5; P＜0.005), MBP (r=0.4; P＜0.01) and hydrocortisone (r=0.3; P＜0.05).
Figure 20 represents the result of research that 14 opera students are carried out, with measured value of the present invention (SA value) as relevant with psychentonia measuring of stress changing.Carry out the measurement of PRP and SA with following interval: after having a rest 10 minutes, attack (spiritual stress test) subsequently.This Figure illustrates the change (Δ SA is to Δ PRP) of PRP and SA.In the psychentonia process, the change of SA and PRP is positively related.
Figure 21 represents the result of research that 14 opera students are carried out, with measured value of the present invention (SA value) as with because the measuring of stress change due to the bicycle test (cycling test).Carry out the measurement of PRP and SA with following interval: after having a rest 10 minutes, attack (bicycle test (bicycling test)) subsequently.This Figure illustrates the change (Δ SA is to Δ PRP) of PRP and SA.In muscle power performance process, the variation of SA and PRP is a negative correlation.
Figure 22 represents the result of research that 14 opera students are carried out, with measured value of the present invention (SA value) as with because the measuring of stress change due to singing.Carry out the measurement of PRP and SA with following interval: after having a rest 10 minutes, attack (singing sow) subsequently.This Figure illustrates the change (Δ SA is to Δ PRP) of PRP and SA.
Figure 23 represents result that 112 continuous patients that make a definite diagnosis ischemic heart desease are studied.Used method is to use β-blocking medicine and measures the book of final entry of SA-value.The result shows do not having significant difference (p＞0.1) aspect the SA measured value between the patient who uses and do not use beta-Blocking agent.
Figure 24. opera solo singer (N=26), in premiere performance period P T meansigma methods (Figure 24 A), HR meansigma methods (Figure 24 B), PRP meansigma methods (Figure 24 C), the variation of MBP meansigma methods (Figure 24 D) and saliva hydrocortisone meansigma methods (Figure 24 E), fiducial limit is 95%.PT:34,45,32 (p＜0.0001); HR:69,84,72 (p＜0.001); PRP:9828,12053,9865 (p＜0.005); MBP:103,107,101 (p＜0.001); Saliva hydrocortisone: 4,5,3 (p＜0.05)
The variation of Figure 25 .PRP and PT.
(A) opera solo singer (N=26), PRP and PT during the premiere performance change (r=0.54, p＜0.0001).
(B): opera student (N=27), PRP during the bicycle exercise test and PT change (r=-0.70, p＜0.0001).
Figure 26. the injury of non-cognitive-ability is retreated and is reflected the occurrence rate in the patient of (NWR): PT＜30 (N=46); 30＜=PT＜60 (N=64); PT＞=60 (N=43).
Figure 27. reliability test.
(A) measure (r=0.94, p＜0.0001) first time of 82 healthy people being carried out PT by HCP.
(B) by HCP 181 continuous patients are carried out PT in the medical clinic clinic and measure (r=0.97, p＜0.0001.
(C): carry out self-PT by 36 non-HCP and measure (r=0.95, p＜0.0001).
Figure 28. the example of the motility of abundant optimal representation of implementing and perfect degree.SO (=WSS is expressed as ◇) is high, and is high when singing audition, and is fine like this because this can be used as with instantaneous stress reality in material circumstance, compare with spirit and the physical sport test of the importance that does not have reality.Illustrate: if the last moment before audition measures, the SO level of then measuring before singing audition may raise.
Good motility water-glass is shown SO and PRP (being expressed as), and the two all raises in addition when singing audition and in spiritual stress test, SO and PRP the two rising level all stress the situation end time fast quick-recovery normal.
When bicycle test, SO significantly reduces along with PRP raises, and when bicycle finishes SO with the reduction of the PRP perfect motility that raises-be expressed as equally.
Figure 29. the example that inadequate optimal representation of possibility and motility level reduce
This curve uses expression SO identical with Figure 28 and the symbol of PRP.
During spiritual stress test, optimal representation may be inadequate.Although stress level raises in process of the test, the heart running reduces, and causes inadequate task performance.When off-test, stress level descends, and the running of heart increases, expression lack motility and to stress self-contradictory cardiophysiology reaction.
After singing audition, with the same at spiritual duration of test, SO raises, and PRP reduces.This has supported the shortage motility, because health obtains having a rest after singing audition, stress level rising-indication lacks mental restoration.
When bicycle test, find the minor variations of SO, although PRP has big variation-be the inadequate other indication of motility thus.
Compare with the colleague who is in equally with being in rest period, the running of heart raises 30%
Figure 30. the stress level of measuring as the WSS when awakening in 12 all introspection processes forms.
SO is in the level (male's normal value＜15) of rising at first.In addition, because the SO measured value is high in first all processes always, can infer that this people is subjected to lastingly stress.
By every day with systematically use instruction herein
Program, the aggregate level of SO (=WSS) finally reach normal level.
Detailed Description Of The Invention
Definition
Before describing the present invention, define the particular phrase relevant with various aspects of the present invention:
Phrase " stress " represent that wherein strain surpasses the strained situation of health resource. Stress be Pleasant, but also can be irritating and be life-threatening sometimes. Having must Will stress two kinds of forms between distinguish: instantaneous with lasting. " instantaneous stress " (that is, " acute stress ") represent prepared physiological status, that is, and when discovering dangerous sign by coming Nerve center/hormone signal automatic state that causes in health from brain. Stress level depends on Individual to the consequence that stimulates expection and the balance between the available resource. Attacking/dangerous sign During end, homeostasis rebulids. If the people has essential resource to use, then can be with positive The cognitive situation of mode. If situation represents wherein strain and surpasses the state of the resource of health, then situation Probably by negatively cognitive. If this latter event continues, then the resource of organism may Becoming bears burdens, and the performance of health reduces. The stress level that raises is expressed as the friendship of rising Feel neural tension force. Yet the rising of sympathetic tone can not represent that stress level raises, as Situation in the slight sports.
Phrase " continue stress " or " chronic stress " be synonym, are owing to Long contact time Instantaneous stress be related nerve center process/hormone and during recover insufficient and cause brain The dysfunction of nerve center/hormone process. It can injure our health.
The activity level of the neural sympathetic division of phrase " sympathetic tone " expression, Can be used as and measure the people on the health and the measuring of the possibility of best performance on the intelligence.
So a kind of situation of phrase " acute stress " expression, wherein the people (is generally at short notice Several hours/several days) experience owing to stress cause the active situation about raising of stomodaeal nervous system.
Phrase " instantaneous stress " is synonym with " acute stress ".
Phrase " lastingly stress " is synonym with " chronic stress ". Preferred term lastingly stress, Because it is being neutral aspect disease term, and " chronic " be used for representing long-term and disease Relevant situation. Find that this is relevant, because if recover subsequently, then light What spend stress not be unsound or insalubrity lastingly. For aspect the term Unanimously, preferred " instantaneous stress " and not preferred " acute stress ".
So a kind of situation of phrase " accumulation stress " expression, wherein the people is (common in long-time Being a few week/some months/several years) experience causes the active situation about raising of stomodaeal nervous system.
Phrase " clinical stress " expression wherein stress cause the situation of clinical symptoms.
The mensuration of phrase " physiology stress " expression sympathetic tone, and because psychology should Swash (=stress) or (=activity induce stress) causes because physiological stress sympathetic tone becomes Do not distinguished between the change.
Phrase " psychology stress " expression stress, and be mainly used in and itself and physics need to be answered Swash in the situation about being distinguished.
Phrase " mechanical stress " expression is owing to sports (just because sports) cause Sympathetic tone increases. Yet, should be emphasized that, during this term is applicable to slightly The degree sports because excessive sports can produce psychology stress.
Phrase " spirit stress " expression since cerebration (just because cerebration) cause Sympathetic tone increases. Yet, should be emphasized that, spirit stress conduction can cause Some people and under some environment stress, and may be for other people or at other Identical people under the environment can not produce stress. Whether the spirit stress test causes and stress depend on The individuality expection of results of stimulation and individual's the balance between the available resources and putting down according to circumstances Weighing apparatus.
Phrase " stimulation " expression can activate mechanoceptor, thermo receptor and/or the sense of skin The stimulation of any type of the receptor that is hurt. Stimulate can be used as mechanical stimulus, thermostimulation, Electro photoluminescence, radiostimulation and/or chemical stimulation provide. Mechanical stimulus can be by for example pressure And/or provide by vibration, thermostimulation can provide by cold and/or hot mode. Electro photoluminescence can provide by for example alternating current and/or galvanic mode. Radiostimulation can Provide example by the infrared ray that for example applies, visible light and/or ultraviolet ray or its combination spectrum As, laser instrument, light emitting diode, infrared light supply, ultraviolet source and/or white light source. Chemistry Stimulation can provide by organic compound and/or inorganic compound.
Phrase " sympathetic tone neutral point " represents on the health or a point in the health, its To the activity level of the sensitiveness of the stimulation that applies and stomodaeal nervous system and/or acute stress Level is irrelevant. This expresses the point that also comprises on the health or in the health, the sympathetic god who wherein raises The threshold value that causes in described some sensitiveness or nociception through tension force and/or stress level is higher.
Phrase " sympathetic tone subordinate point " represents on the health or a point in the health, its In the sensitiveness of the stimulation that applies depended on be the activity level of stomodaeal nervous system to raise Sympathetic tone or the stress level of rising cause that this point shows sensitiveness and/or wound The threshold value of evil impression reduces.
Apparent from the disclosure, sympathetic tone neutral point and sympathetic tone subordinate point Anatomical location be not important. When utilizing therein implanted device to stimulate, this point should This be health " in ", and use hand gear to stimulate typically health " on " one Individual point.
The indicate intensity of stimulation that known point is applied of phrase " threshold value of stimulation ", its purpose The stimulation that is that the people is perceived and applies is not pleasant, and more specifically saying so makes the people displeased Fast or pain.
Phrase " threshold value of pressure sensibility " is indicated to the intensity of known point applied pressure, It is not pleasant that its purpose is to make the people to perceive applied pressure, and more specifically saying so makes Offending or the pain of people.
Phrase " nociception threshold value " when being illustrated in this threshold value the people in the stimulation of each perception be Nocuous, that is, and disorganization's property. This expression comprises that also the people is perceived as uncomfortable thorn Swash.
Phrase " basically simultaneously " different measurement (for example, calibration threshold value and the stimulus thresholds of expression Measurement) in the time period of a few minutes, carry out, for example, one minute, two minutes, three minutes, Five minutes, ten minutes, 15 minutes.
Phrase " significantly lower " refers to that the nociception threshold value of sympathetic tone subordinate point is to hand over Feel neural tension force neutral point threshold value at the most 85%, particularly at the most 80%, more particularly for extremely Many 75%.
Expression that phrase " is used for applying and measuring the system of stimulation " can apply and measure stimulation System, for example a device or several device.
Phrase " pressure sensibility device " expression can apply the device with gaging pressure.
The method of phrase " label " expression mark measurement point.
The point that phrase " measurement point " expression is such, for the stimulation that applies, its stimulation Threshold value is neutral or depends on sympathetic tone.
Express " C.V.17 ", " Per 1 " and " St 18 " represent to meet routine Theory of traditional Chinese medical science (Beijing College of Traditional Chinese Medicine: Essentials of Chinese Acupuncture, Beijing Foreign Languages Press, 1980) meridian point (meridian point). C.V. be conception vessel; Per is the heart Bag, St is stomach. The C.V.17 point, i.e. gray shade district shown in Fig. 3 is wherein at this ash In the C.V.17 in look shadow region according to the present invention the point of frequent use be expressed as stain. Per 1 Point, i.e. gray shade district shown in Fig. 1 is wherein 1 interior of the Per in this gray shade district According to the present invention the point of frequent use be expressed as stain. St 18 points, i.e. ash shown in Fig. 4 The look shadow region is wherein in the interior the most frequent use according to the present invention of the St 18 in this gray shade district Point is expressed as stain. Described each point (C.V.17/Per 1 and St 18) is according to its traditional Chinese medical science life Name fully limits, and is the form of the point on the body surface. In Fig. 1,3 and 4, provide To come actual area and this point that mark will check only be because it is when stimulating in the gray shade district The character of the point of pain limits. This also means, this point may be on accompanying drawing mark The gray shade district outside. In fact, described point can be positioned at corresponding to being fed to sympathetic nerve Any position in the parts of skin at the heart place of system (as for example below with reference to described in the document, Rutherford J.D., Braunwald E.﹠ Cohn P.F., " Chronic heart Disease "; Braunwald E., ed. " Heart Disease.A textbook of Cardiovascular Medicine " .Philadelphia:W.B.Saunders Company, 1988; 1314-67; Williams P.L., Warwich R., Dyson M.﹠ Bannister L.H., eds.Gray s Anatomy.New York:Churchill Livingstone, 1989; 723-1168; Mann, F., " Textbook of acupuncture ", William Heinemann medical books, London 1987; 57-64).
Express " TH 3-6 " with " TH 10-11 " represent respectively on the thoracic vertebrae of identical numbering Spinous process 3-6 and spinous process 10-11. Spinous process is to touch up the part that resembles the knur sample on the backbone. Spinous process 3-6 and spinous process 10-11 are illustrated among Fig. 2, and spinous process 3-6 is four the highest on the backbone Black round dot, spinous process 10-11 are epispinal two minimum round dots.
" warning system sensitiveness " or " WSS " warning system of expression CNS control, It works to be based upon performance or the police of the enhancing in stress situation by stomodaeal nervous system Guard against. Thus, the rising of WSS always is attended by the rising of sympathetic tone, and sympathetic nerve Tension force raise the rising may not be attended by WSS (for example the rising of sympathetic tone be because The physiology that sympathetic tone is raise needs, for example when light to moderate sports). Discovery of the present invention shows that the overall rising of WSS is attended by on the health or the interior sympathetic nerve of health The tenderness of tension force subordinate point raises (nociceptive threshold value reduction), means to show this tenderness The indication that the measurement result of the present invention that raises provides WSS sensitiveness to raise.
Phrase " defense reaction/reflex sensitivity " or " DRS " the non-understanding of expression CNS control The defense system that sexual reflex is regulated, its and the sympathetic nervous system WSS that unifies is relevant, so that foundation The defense reaction that strengthens. Thus, the rising of DRS always is attended by sympathetic tone and WSS Rising, and sympathetic tone raises and may not be attended by the rising of DRS (for example at sympathetic nerve The rising of tension force is the physiology needs that raise owing to sympathetic tone, for example slightly arrives During the moderate sports). Discovery of the present invention shows that the overall rising of DRS is attended by on the health Or the tenderness of sympathetic tone subordinate point raises (nociceptive threshold value reduction) in the health, meaning Distinguishing the flavor of and showing that the measurement result of the present invention that this tenderness raises provides DRS sensitiveness to raise Indication.
The phrase of using in measuring process " injury retreat reflection " is used for representing that eyes, cheek are (frightened Frighten reflection) the imperious contraction of muscle in the zone or the musculus flexor of neck and upper limbs imperious Contraction of muscle.
Organism carries out in response to environmental evolution in phrase " neural flexibility " expression The ability of suitably adjusting, that is, and reaction size and the regeneration rate of corresponding passion condition. Good spirit Active expression organism responds this variation fast and fully and makes adjustment. For instantaneous Stress concrete condition, this refer to that stress reaction is fully activated at the peak place of performance and Rebuilding body inner equilibrium rapidly when this situation finishes. The degree of flexibility be lastingly stress level Useful measuring, flexibility lacks the increase that multilist more shows lasting stress level.
Preferred implementation
Total resources in order to ensure the people obtain best utilization, and given stress arousing in the situation, importantly, this can be guaranteed by the neural functional level of measuring any preset time.
Method of the present invention is behaved provides this instrument, and described instrument is the method for measuring the level of activation at once of sympathetic nervous system in form:
1) low measured value is represented the low level of activation of sympathetic nervous system, and is the best probability basis that stress situation make best reply with future thus.
2) one high measurement value provides following information for the user, and promptly from angle of physiology, the people is in so-called stress stage " transferred the resource of organism in order to tackle brain to be perceived as situation dangerous or potentially dangerous.
3) multiple high measurement value provides following information for the user, promptly, the people is in secular " stress stage ", and it can produce the resource of organism and consume in the long run, and be provided on the intelligence, on the health, on the emotion and socially go up the basis that functional level reduces.
4) height of Gai Bianing and low measured value provide following information for the user, and promptly the people is in wherein " stress stage " and is alternately activated and the situation of deactivation.As a result, have the probability of study and awareness (awareness).
In specific embodiment, thus this method and special instrument are associated, and can teach the people based on the educational procedure of actual measured value and how prevent and dispose passive stress and to tell that he specifically is what makes its stress level rising/reduction.
The present invention be to be used for determining the level of activation of sympathetic nervous system and thus the people on the health and the result that furthers investigate of the method for the probability of putting up the best performance on the intelligence, and solved the problem of measuring the known method of sympathetic tone dexterously, described known method is measuring of sympathetic nervous system level of activation clearly, and being called as the psychology relative with mechanical stress in this article stress.
According to the present invention, find surprisingly, have some such points at health, the threshold value of described point is that sympathetic tone is neutral when these points being applied stimulation, even can react by analgesia, and other point is the sympathetic tone subordinate, with reference to above-mentioned definition-also discovery in addition, only situation is only like this when sympathetic tone is associated with the state of WSS and/or DRS, and the tenderness rising that the sympathetic tone that causes owing to for example simple light to moderate sports raises and do not cause sympathetic tone subordinate zone/subordinate point.In other words, have some point, its level of activation to the sensitivity of the stimulation that applies and sympathetic nervous system is irrelevant, perhaps sympathetic tone/the stress level of Sheng Gaoing is induced analgesia, and also have some other point, its sensitivity to the stimulation that applies depends on the level of activation (when the level of activation of sympathetic nervous system depends on WSS/DRS) of sympathetic nervous system, and promptly these points can the hyperpathia that becomes in response to the rising of sympathetic tone and/or stress level and/or WSS/DRS level.Therefore, according to the present invention, when the level of activation of sympathetic nervous system raise with the rising of WSS/DRS, people's sympathetic tone subordinate point also raise to the sensitivity of the stimulation that applies.This understanding is surprising, stress increase tolerance level (Amit andGalina, Physiol.Rev.66:1091-1120,1986) to pain usually with the sympathetic tone that raises thus because former description is thought.Therefore, the sympathetic tone subordinate point of Que Dinging with react about the known different modes of health generally.In fact, the sympathetic tone subordinate point of determining is that the sympathetic tone that wherein stress and/or raise can show as and influences hyperpathia (promptly, sensitivity raises or nociception raises) those, this forms contrast with inductive analgesia of sympathetic tone by stress or raising of proof in the past.
By measure the sympathetic tone neutral point obtain the required intensity that applies stimulation of stimulus threshold and with its with compare at the required stimulus intensity that applies of the identical stimulus threshold of sympathetic tone subordinate point acquisition, obtained the physiological measurements (and being the physiological measurements of sympathetic tone sometimes) of WSS/DRS, obtain thus the people psychology stress or instant stress level.This measured value can be regarded as the measurement result at once of WSS level.
Using method of the present invention to determine secular, instant or when acute stress level and/or WSS/DRS state, this method is behaved provides the instrument that is used to adjust stress state and optimizes its performance thus.The acute rising of sympathetic nervous system level of activation may have favorable influence to people's performance.Therefore, be well known that rising the epinephrine level may to the performance optimization favourable.Therefore, method of the present invention is used to adjust sympathetic tone, so that obtain the sympathetic nervous system level of activation of rising, thereby produces favorable influence.
It is also important that the following ability of method of the present invention, be that described method makes it in the rising that is not realized of the WSS/DRS that causes the people or reduction (for example also may be used to determine, stress or stress observe lastingly as instantaneous) in environment or the factor of life style, if because method of the present invention allow to measure repeatedly WSS/ stress level-people's log in the time period of this replication, then also the dependent event of daily life may be associated with measured value, thus promote stress induced factor determine and reduce stress activity/action.
Therefore, provide the method for measuring the instant level of activation of sympathetic nervous system and/or stress level and/or WSS and/or DRS level, described level of activation is significant for the ability or the probability of people's optimal representation.Described method may have the character of diagnosis and have diagnostic value, but also may be used as method of prognosis, be its behaviour provide instant probability that the people puts up the best performance and thus prevention be lower than the prognosis of best performance, as mentioning in the background technology, in so-called " stress ", sympathetic nervous system is transferred the resource of organism, makes to deal with actual dangerous situation/attack in the possible mode of the best.It is faster and more clear to this means that the people thinks deeply on intelligence, and the ability that is primarily focused on simultaneously in its thinking increases.In order to support this purpose, stoped incoherent sensory impression effectively.On the health, health is by shortening the response time, increase muscle strength, the coordination between oxyesthesia and optimization thinking and the motor skill being responded.
The test that the healthy people of 146 random chooses is carried out shows, at 79 philtrums that seriously stress (the stress group level 3 as defined below), have half (41 people) think they oneself do not have stress/have very low stress.As a result, method of the present invention and survey tool provide by behaviour otherwise important information that this people can not learn has huge real value.
As mentioned above, method of the present invention can also be used for writing down in secular mode the level of activation of the level of activation of sympathetic nervous system and WSS thus and/or DRS, and therefore causes that for this state of timely prevention the complication that stress be correlated with is effective.This record can for example be sent to the central register/data center of monitoring personal data, and in time the individual is sent back in warning, thereby can avoid described complication.
According to the present invention, the stimulation sensitivity of each point can make a marked difference between different people, and the unitary determination value for sympathetic tone/WSS/DRS of a people can not be associated with this people's actual stress state inevitably, unless known this people's normal condition.Therefore, may need the unitary determination value of sympathetic tone/WSS/DRS to be replenished with additional information.Therefore, low sympathetic nervous system/WSS/DRS level of activation and measure repeatedly between little difference represent the prognosis utilization of optimum of this people's resource.Yet, high activity level and measure repeatedly between little difference be not clear and definite, and need additional information.Therefore, the situation of high activity level can take place wherein to have measured by described method, and by mode that stress form (application form) carry out supplement Analysis show this people do not show clinical stress sign.In this case, measured value may reflect: 1) instantaneous stress and/or persistent chronic stress, perhaps can reflect 2) people do not recognize lastingly stress of clinical symptoms of stress.Back one situation can be observed in the people with serious lasting stress level.Complementary testing about motility can be distinguished between two kinds of situations: high motility water-glass let others have a look at be subjected to instantaneous stress, and inadequate motility can represent that the people is subjected to lastingly stress (referring to Figure 28-30).Wherein high WSS/DRS value and low WSS/DRS value combination and short situation of time is represented, high measured value reflection and instantaneous situation that stress be relevant, and lastingly stress level be low (referring to Figure 28-29).
Yet, for many actual purposes, what be fit to is to measure to have represented colony (for example, the calibration threshold value of the varying level the background about age, sex and ethnic group), determine the individual stress level and/or the probability of sympathetic tone because this provides by a single measurement carrying out stimulus threshold, thereby no longer need to carry out the measurement of calibration threshold value.
Therefore, calibration threshold value can not be self-metering numerical value, but measure in advance or predetermined value, promptly based on the numerical value of a people or a big group people's previous observed result.
According to the present invention, stimulation can be the stimulation that activates any kind of the equivalent sensor of (for example, in periosteal tissue (periostal tissue)) in mechanoreceptor, heat sensor and/or the nociception sensor of skin or the health.Stimulation can be used as mechanical stimulus, thermostimulation, electricity irritation, radiostimulation and/or chemical stimulation to be provided.Mechanical stimulus can provide thermostimulation to provide by cold and/or hot mode by for example pressure and/or by vibration.Electricity irritation can provide by for example alternating current and/or galvanic mode.Radiostimulation can provide by the infrared ray that for example applies, visible light and/or ultraviolet or its combination spectrum, for example, and laser instrument, light emitting diode, infrared light supply, ultraviolet source and/or white light source.Chemical stimulation can provide by organic compound and/or inorganic compound.
Also might be directly and polymorphism receptor cell or spread out of motor neurocyte and interact, with reference to following detailed description.Can cause that maybe the chemicals that neurocyte excites stimulates these cells with AC or DC, neurotransmitter.
The physiological measurements of the sympathetic tone of record is total measured value of people's acute stress level and people's accumulation stress level sum (that is, WSS and/or DRS).Method of the present invention also allow to write down any intervention/reduction stress active influence.
When the specific point to the people applied stimulation, its stimulation that no longer will apply was perceived as comfortable, more particularly, and the threshold value that the stimulation that this people will apply obtains stimulating when being perceived as irritating or pain.In addition, the measured value that polymorphism receptor cell that can be by measuring sympathetic tone subordinate point or the excitation threshold that spreads out of motor neurocyte obtain being correlated with.
The sympathetic tone neutral point also can be expressed as calibration point.These points may be positioned at the front of clavicle upside and the back of spinal column, are expressed as TH 10-11 particularly.Described point also may be positioned at any position on finger or the toe, but preferably on the back side of finger or toe.
Sympathetic tone subordinate point also can be expressed as measuring point.These points can be arranged in innervation ground corresponding to sympathetic nervous system to the innerv skin of heart/any position of skin, for example relate to following three in front: at the intermediary C.V.17 of breastbone, ST 18 and the Per between nipple and anterior axillary fold 1 between inframammillary two ribs, and relate in the back with omoplate between the zone TH 3-6 corresponding.According to an embodiment, preferably select the pain spot of described point, this point makes the most accurately expresses level of activation.
The present invention allows to measure generally the acute stress of people in the short time (for example several hours/several days), and the accumulation of long-time (for example some months/several years) stress.
Can by technology well known by persons skilled in the art instantaneous stress and lastingly stress between distinguish.These technology include but not limited to: about the talks of people's physiology and mental status or wherein can randomly stress illustrate other method of its state by form (application form) by filling out.In addition, can by technology well known by persons skilled in the art find stress reason.These technology include but not limited to: about the talks of people's physiology and mental status or wherein can be randomly by fill out stress/the equilibrium of stock table illustrates other method of its state.These technology include but not limited to the WSS/DRS of individual repeated measurement is combined with relative daily record.This mentioned as the replenishing of additional information of assay method of the present invention simply at preamble.Also might the monitor in a period of time level of activation (by continuous measurement heart rate, blood pressure etc.) and allow this people's record relate to the detailed daily record of following content: 1) WSS/DRS, 2) incident, 3) thinking, 4) emotion and 5) individual that determine with clinical symptoms stress be relevant, with the cognition of itself and gained information handle combined meeting be provided for distinguishing instantaneous stress with lastingly stress answer.
Also might comprise special manoeuvring test.These technology include but not limited to: carry out spiritual stress test, sports tests (for example, bicycle exercise test) and/or the performance test (referring to Figure 20-30) relevant with people's professional life.The various aspects of test have reflected motility: to the degree of the stress that stimulates and the speed of recovering subsequently.
First clinical indication of chronic stress is that the muscle tone in tired and the locomotor muscle raises.It can show as for example headache, and the pain of back, shoulder and cervical region.This state be harmless and perceive actively stress many situations in experience.
In secular situation about stress load, in the neural part (that is autonomic nervous system) that is not under the will power driving, cause other symptom.These symptoms can show as for example poikilothymia, stomachache, heart beating and be difficult to concentrate.
Further increase the weight of if stress load, then cause the other symptom except that above-mentioned symptom in the part of the nervous system under will power drives.For example, the people no longer can control its indignation or dysphoria, and negatively influences its social behavior.
The measured value that obtains the required intensity that applies stimulation of stimulus threshold can use the system of the intensity that can measure the stimulation that applies to measure.An example that is used to measure this system of the stimulation that is applied is to measure the system of the mechanical stimulus that is applied, the thermostimulation that is applied, the electricity irritation that is applied, the radiostimulation that is applied and/or chemical stimulation.The system that is used to measure the mechanical stimulus that is applied can be the device that for example is used to measure institute's applied pressure, and described device for example is a piezometer.Using after the device for example can measure institute's applied pressure tests, can obtain the measurement of the required intensity of being exerted pressure of pressure sensibility threshold value with finger.
Method of the present invention can be used as the measuring method of the power of influence of comings and goings in addition.These activities may be relevant with the occupational health therapy or uncorrelated, for example can comprise and be perceived as the corresponding activity of situation about stress arouse.
Method of the present invention can be implemented by the people different with the measured, is perhaps implemented by the measured.When measuring, the measured obtains the most accurate measured value.
Now, comprehensively research shows, can be by the activity level (horizontal 0-3) of following mode with sympathetic nervous system, with respect to the stimulation that obtains the required form of exerting pressure of uniform pressure sensitivity threshold value at sympathetic tone subordinate point, be associated with the stimulation of the required form of being exerted pressure of the pressure sensibility threshold value that is used to obtain the sympathetic tone neutral point:
Level 0: be greater than or equal at the uniform pressure sensitivity threshold value institute applied pressure of sympathetic tone neutral point 80% o'clock at the pressure sensibility threshold value institute applied pressure of sympathetic tone subordinate point.
Level 1: the pressure sensibility threshold value institute applied pressure of sympathetic tone subordinate point between the uniform pressure sensitivity threshold value institute applied pressure of sympathetic tone neutral point 55% and be lower than 80% between the time.
Level 2: the pressure sensibility threshold value institute applied pressure of sympathetic tone subordinate point between the uniform pressure sensitivity threshold value institute applied pressure of sympathetic tone neutral point 30% and be lower than 55% between the time.
Level 3: be lower than at the uniform pressure sensitivity threshold value institute applied pressure of sympathetic tone neutral point 30% o'clock at the pressure sensibility threshold value institute applied pressure of sympathetic tone subordinate point.
With respect to the uniform pressure sensitivity threshold value institute applied pressure in the sympathetic tone neutral point, the level of activation of sympathetic nervous system can be different with different people with the above-mentioned ratio between the pressure sensibility threshold value institute applied pressure of sympathetic tone subordinate point.In some cases, deviation can be about 90% to the maximum.
For same individual, measured value can be in addition between the different sympathetic tone subordinate points and between different sympathetic tone neutral points and different.Therefore, in order to obtain the most accurate sympathetic nervous system level of activation measured value, importantly selecting can be owing to other former thereby responsive sympathetic tone neutral point.
Also find to be applicable in the situation of use thermostimulation, electricity irritation, radiostimulation or chemical stimulation at required institute's applied pressure of the pressure sensibility threshold value that obtains the sympathetic tone neutral point and above-mentioned dependency between the required institute's applied pressure of the uniform pressure sensitivity threshold value that obtains sympathetic tone subordinate point.For example, have been found that when using applied pressure, sympathetic tone subordinate point is more responsive to for example hot and cold, and described heat is for example by conduction of heat or radiant heat transfer, described point also than sympathetic tone neutral point to more responsive from the influence of organic compound and/or inorganic compound.
Can be used in combination any sympathetic tone neutral point with any sympathetic tone subordinate point.The preferred combination of using the sympathetic tone neutral point front or the back and sympathetic tone subordinate point.For example, preferably be used in combination the sympathetic tone neutral point of the front on the clavicle upside with sympathetic tone subordinate point C.V.17 or St 18 or Per 1, perhaps preferred and sympathetic tone subordinate point TH 3-6 is used in combination sympathetic tone neutral point TH10-11.
Therefore, the present invention relates to measure the method for the state of experimenter's sympathetic tone and/or stress level and/or warning system sensitivity, may further comprise the steps: measure stimulation that applies with stimulus threshold and the stimulation that applies with same threshold at one or more sympathetic tone subordinate point measurements in one or more sympathetic tone neutral points, perhaps measure the stimulation that applies with threshold value at one or more sympathetic tone subordinate points and randomly with described threshold value with measure in advance or predetermined calibration threshold value compares.Typically, the threshold value of described stimulation is the nociception threshold value in the stimulation at relevant stimulation point place.
According to a specific embodiment of the present invention, the stimulation that is applied can provide by applying mechanical stimulus, thermostimulation, electricity irritation, radiostimulation and/or chemical stimulation.
According to a specific embodiment of the present invention, can provide mechanical stimulus by exerting pressure.
According to a specific embodiment of the present invention, can provide mechanical stimulus by applying vibration force.
According to a specific embodiment of the present invention, can be by applying thermal source or low-temperature receiver provides thermostimulation.
According to a specific embodiment of the present invention, can provide electricity irritation by alternating current that applies or the unidirectional current that applies.
According to a specific embodiment, radiostimulation can be by the infrared ray that for example applies, visible light and/or ultraviolet or its combination spectrum, and for example, laser instrument, light emitting diode, infrared light supply, ultraviolet source and/or white light source provide.
According to a specific embodiment of the present invention, can be by applying organic and/or inorganic compound provides chemical stimulation.
According to a specific embodiment of the present invention, can be undertaken by the system that is used to measure the stimulation that is applied with the mensuration of the stimulation that threshold value was applied that stimulates.
According to a specific embodiment of the present invention, can be in front carry out and/or on corresponding to the spinal column of TH 10-11, carry out with the measurement of the stimulation that stimulus threshold was applied of sympathetic tone neutral point at rear side at the upside of clavicle, and/or on finger and/or carry out on the toe; On finger and/or in the situation of carrying out on the toe, the preferred stimulation that applies is carried out on the back side of finger/toe.
According to a specific embodiment of the present invention, measurement with the stimulation that stimulus threshold was applied of sympathetic tone subordinate point can be carried out to the one or more positions on the innerv skin of heart corresponding to sympathetic nervous system on innervation ground, for example at one or more points of the front that relates to following three positions: at the intermediary C.V.17 of breastbone, ST 18 and the Per between nipple and anterior axillary fold 1 between inframammillary two ribs; And, wherein select the pain spot of described point in the back corresponding to one or more points of TH 3-6 in zone between the omoplate.
According to a specific embodiment of the present invention, the present invention relates to quantitatively and/or qualitative determination comprises people's the sympathetic tone of animal and/or the method for stress level and/or WSS and/or DRS level, described method comprises
A) stored calibration threshold value and stimulus threshold, described calibration threshold value is the quantified measures of the nociception threshold value of sympathetic tone neutral point on the animal health or in the health, and described stimulus threshold is the quantified measures of the nociception threshold value of sympathetic tone subordinate point on the animal health or in the health;
Calculate the readout of sympathetic tone and/or stress level and/or WSS and/or DRS level by stimulus threshold is compared with calibration threshold value, thereby described readout is the measuring of sympathetic tone and/or stress level and/or WSS level in this animal.
In one embodiment, calibration threshold value and stimulus threshold are simultaneously-measured basically.Yet described calibration threshold value also can be represented based on the resulting history average of former measurement or predetermined value steady state value for example, such as the meansigma methods that can represent many different people.In certain embodiments, described calibration threshold value is set to zero.
When the calibration threshold value that use pre-determines or measures in advance, the purpose of making is to help the inventive method for to user-friendly method like this, obtains stress level and/or sympathetic tone indication simple and that be easy to get because it needs to carry out a single measurement.
In any case the readout of preferred sympathetic tone/stress level is the mathematical combination of calibration threshold value and stimulus threshold.This means that the readout of described method is by the numerical value that stimulus threshold and calibration threshold value mathematical combination are obtained (or other α-numeral indication, for example colour coding, tone etc.).Typically, described mathematical combination is the mathematical function (being generally monotonic function) (that is, with the function of calibration threshold value divided by stimulus threshold) between calibration threshold value and the stimulus threshold.Yet described mathematical combination thing can also be the function of the difference of two numerical value.
It is to be noted, even carry out in fact like this according to the present invention, do not need these two threshold values to be to use identical measurement unit to measure yet, and even can imagine that (although being so not practicable) two threshold values are the threshold values with respect to the different stimulated type.
In embodiments, nociception is by accepting pressure, heat, cold, radiation, chemical stimulation or its combination and inductive.
According to an embodiment, significantly reduce this people of expression at the nociception threshold ratio of sympathetic tone subordinate point in the sympathetic tone neutral point and have the sympathetic tone rising relevant with WSS/DRS.
The sympathetic tone readout of measuring is record at once, perhaps record in long-time.Therefore, specific embodiment relates to the method for wherein readout of sympathetic tone being compared with the sympathetic tone readout of mensuration before at least one, the sympathetic tone of the time point that described numeric representation in the past is former.
The various uses of the inventive method
Because above-mentioned method can provide sympathetic tone and/or stress level and/or WSS and/or DRS level quantitatively and/or observation measurements, many treatments (medical science with antimedical) method that described method and wherein treatment effectiveness might be depended on to a certain extent the patient's who accepts this particular treatment sympathetic tone and/or stress level combines.
Known numerous disease state is relevant with the variation of sympathetic tone, it also can directly help disease (for example, ischemic heart desease, hypertension) pathogeny or as the consequence of constitutional disease (for example, pain, endocrinological disease, psychology disease).In both cases, method of the present invention can be used for accurately monitoring that to be used for the treatment of constitutional sick or be used to alleviate the effect of any pharmacological intervention that the symptom relevant with principal disease write out a prescription.For patient and/or doctor, this measurement provides measurable reading, and the effectiveness of its permission patient monitoring pharmacological treatment and the variation for the treatment of in the case of necessary are so that provide the therapeutic outcome of optimization.
Therefore, the invention provides the method for the progress of the therapeutic scheme that is used to control the patient (medicine, operation or pass through alternate manner), the effectiveness of wherein said scheme and/or patient's compliance depend on described patient's sympathetic tone and/or stress level and/or WSS and/or DRS level, and described method comprises
I) during therapeutic scheme one or many measure described patient's sympathetic tone and/or stress level and/or WSS and/or DRS level and
Ii) be benefited and the composite measurement result of the measurement result of step I adjusts therapeutic scheme from described therapeutic scheme according to the patient.Preferably, step I is implemented by one of described method that is used to measure sympathetic tone and/or stress level and/or WSS level herein.
Term " patient is benefited and the composite measurement result of the measurement result of stress level/WSS and/or DRS from described therapeutic scheme " expression about the information of patient's comprehensive and/or specific medical condition, patient stress/equilibrium of stock and disclosed herein stress/in fact WSS/DRS horizontal survey result and evaluate patient defer to or the combination of the information of the degree of the therapeutic scheme accepted.In other words, with disclosed by the invention be used to measure sympathetic tone and/or stress/method of WSS/DRS level is with being used to estimate the effect of therapeutic scheme or the more conventional approach and the measuring method of compliance used, so that realize the more exact evaluation to described effectiveness and/or compliance.
The enhanced example of expection pharmacology's compliance during the treatment of following non-limiting therapeutic scheme group: use the treatment (selective serotonin reuptake inhibitor) of SSRI; Psychopharmacology psychology, spirit or conduct disorder that is subjected to influence is treated, and comprises depression, other emotionally disturbed, addiction, dependent conditions, neurosis and suicide; Progress on Insulin Treatment in Diabetes; As the Nicotine replacement therapy of the auxiliary treatment of giving up smoking, the hormone therapy of post-menopause syndrome; Hormone or other Therapeutic Method about reproduction, fertility and miscarriage treatment; The anti-inflammatory agent treatment of acute and chronic inflammation; The anti-infective therapy of infectious disease; The treatment of the hypothyroidism or the hyperthyroidism patient's condition; Treatment about Dental Hygienist; The treatment of using cardiovascular drugs to carry out to heart, blood vessel and kidney disease; Use gastrointestinal drug to ulcer, irritable bowel syndrome, malabsorption, feel sick and treatment that other symptom is carried out; The pharmacological treatment that the medicine of use reduction body weight carries out; Exercise plan; Loosen plan; Diet program; Consulting or guidance; Stress governing plan; Individual Development Plan; The performance plan; With self-nursing care plan.
Especially, method of the present invention uses the purposes aspect the treatment that SSRI carries out to be based on the surprising discovery of being finished by the inventor recently in control.In general, women's cancer patient of new diagnosis shows very high stress level/WSS (the pain stimulus threshold level that shows as sympathetic tone subordinate point reduces) that the application of the invention disclosed method is measured, but observe and have only a female patient, the difference of the female patient that she and other are checked is that she has received the SSRI treatment, this female patient shows significantly reduced stress level/WSS, is suffered from metastatic carcinoma although she newly is diagnosed as.In addition, women's cancer patient's general situation comprises the existence of NWR, and this does not find in the women of SSRI treatment.
Just as discussed above, also might with of the present invention be used for stress/ purpose that the WSS/DRS method for measuring is used to intervene.Therefore, the invention still further relates to be used to prevent undesirable or do not have effect stress method, described method comprises
A) by use described herein method measure the patient sympathetic tone and/or stress and/or WSS and/or DRS level,
And if sympathetic tone and/or stress level and/or the WSS and/or the DRS level of the demonstration of the measured value among step a rising, the sympathetic tone subordinate point on the patient body or in the health is stood in a period of time than the more low intensive stimulation of stimulus threshold.
This specific intervention can be used for for example treating bearing seriously and stress and be in the patient that must treat immediately.Yet, also might in so not critical case, use more long periods of treatment scheme, wherein said method comprises after step a in addition,
B) measure patient's sympathetic tone and/or stress level by method disclosed herein, if and this new measured value does not show sympathetic tone and/or stress level that the rising degree is lower, then make sympathetic tone subordinate point in a period of time, accept the stimulation that reduces than stimulus threshold intensity, the described time period different with the time period described in the step a (preferably longer) and
C) repeating step b shows sympathetic tone and/or the stress level lower than step a rising degree up to measured value.Convenient and especially practical is, not in the situation of intervening by skilled doctor therein, stimulus intensity that sympathetic tone subordinate point accept to reduce can be shown by visible or audible indicating mode proofread and correct stimulus intensity-like this, avoid stimulating becoming insufficient or too strong.Certainly, this embodiment requires to comprise system or the device that is used for by the equipment of the sensing stimulus intensity of patient or doctor's use.
This embodiment can comprise makes the stimulus intensity of sympathetic tone subordinate point acceptance reduction control by closed-circuit system, described closed-circuit system can stimulate the polymorphism receptor cell and can measure from described polymorphism receptor cell and/or with the muscle protective reflex and react the relevant pulse of importing into that spreads out of motor cell, about the details of this system, referring to following content.
Also might prognosis use the present invention in following method, described method comprises
1) mensuration patient's sympathetic tone and/or stress level, and subsequently
2) provide patient's prognosis about this disease by the measurement result of incorporating step 1 in the measurement result of prognosis into, the measurement result of step 1 shows that sympathetic tone and/or the low then expression of stress level/WSS/DRS and the measurement result of step 1 show that higher sympathetic tone and/or stress level/WSS/DRS are in a ratio of better prognosis.Equally, the preferred mensuration by method execution in step 1 disclosed herein.Therefore, also might in prognosis, make in this way, because might intervene poor prognosis generally now and/or be in patient in the danger that forms specified disease situation and/or disease.
Preferred described disease is selected from following group:
Acute, the subacute or chronic struvite patient's condition;
Wherein immunoreation state that human organs is damaged or wherein inadequate function of immune system cause the state of the impaired and/or disease of function;
Acute, subacute or chronic infectious disease;
Be subjected to the cardiovascular disorder of sympathetic tone influence, for example cyclical shock, atherosclerosis, thrombosis, the ischemic patient's condition, infraction, arrhythmia, hypertension;
The vegetative growth disorder;
Acquired metabolism disorder;
Poison or because the somatic damage that machinery, heat, electricity or radiant energy cause;
Be subjected to the disorder of psychology, spirit or the behavior of sympathetic tone influence, for example the dependent conditions of depression or other emotionally disturbed, addiction or any kind, neurosis, suicide, sleep disordered, tired, have psychological and/or mental characteristics and a complaint stress be relevant;
The fertility of masculinity and femininity reduces;
Be subjected to gynecological's obstacle of sympathetic tone influence, for example premenstrual tension syndrome, dysmenorrhea, climacteric problem, hyperemesis gravidarum, preeclampsia and convulsions, premature labor, situs inversus viscerum (situsinvertus), induction of labour, postpartum hemorrhage;
Be subjected to the otolaryngology disorder of sympathetic tone influence, for example tinnitus and presbyacusis;
Be subjected to the dermatological obstacle of sympathetic tone influence, for example pruritus;
With the gastrointestinal disease of stress sensitive clinical sign and symptom, for example gastric duodenal ulcer, irritable bowel syndrome, malabsorption, diarrhoea, constipation, nauseating and vomiting;
Neurological disorder, for example tension headache, migraine, cerebral concussion, hypercortisolism, parkinson, Alzheimer, intracranial wound and neuropathy;
Endocrine regulation, for example diabetes, hypothyroidism, hyperthyroidism, adrenal cortex disorder, adrenal medulla disorder, hypothalamus disorder (hypothamicdisorders), hypophysis disorder and polycystic ovary syndrome;
Allergy for example is reflected at the allergy in skin, bronchus and the gastrointestinal tract;
With the lung disease of impaired gas exchange, for example bronchitis and emphysema;
The disease of joint and bone, for example acute or chronic arthritis and osteoporosis;
Form the relevant disorder of change, for example obesity, body weight loss, cachexia with body weight;
Sodium and the water storage property stayed morbid state, for example heart failure, renal failure, liver failure; With
Pain.
Especially an interesting embodiment of the present invention is based on following discovery, that is, of the present invention be used for measuring stress/method of WSS/DRS and/or sympathetic tone is relevant well with the known measuring method that is used for myocardial oxygen consumption.Therefore, the invention provides the method for the myocardial oxygen consumption that is used to measure the experimenter, described method comprises that the method according to this invention is measured the experimenter and based on measuring the level of myocardial oxygen consumption with the predetermined dependency of sympathetic tone measured value.It is significant that this dependency has proved, and is at " pressure speed the product " (product of systolic pressure and heart rate; With reference to Opie LH.Normal and abnormalcardiac function:in Heart Disease.Braunwald E, Zippes DP ﹠amp; Libby P. (ed): W.B.Saunders 2001 (6th ed): 468-469; With NobleRE:Diagnosis of stress:Metabolism 2002; 51 (5): 37-39)) it is relevant to have significance between measured value and the measured value of the present invention; Therefore, the dependency between preferred myocardial oxygen consumption and sympathetic tone or the WSS/DRS is based on the predetermined dependency between sympathetic tone measured value and PRP (the pressure speed product) measured value.
PRP reflects the blood supply of heart, and reflects the ability to work of heart thus.It also reflect stress degree.PRP has formed practical heart oxygen picked-up index, and reflects the duty of heart thus.Heart can increase by increasing heart rate, heart wall stress and myocardial contraction the needs of oxygen, (Opie LH.Normal and abnormal cardiac function:in HeartDisease.Braunwald E, Zippes DP can take place in these before ischemia takes place the ischemic heart patient; Libby P. (ed): W.B.Saunders2001 (6th ed): 468-469.).The oxygen picked-up is regulated by the beta-adrenergic catecholamine.Similarly, it is the useful active indicant of cardiac sympathetic nerve, and degree (the Noble RE:Diagnosis of stress:Metabolism 2002 that indicates the physiology of heart to load thus; 51 (5): 37-39).
Another interesting embodiment of the present invention is based on following discovery, that is, the method for the application of the invention, might psychological stress and health stress between distinguished.Therefore, shown that the measured value (SA level) that obtains according to the present invention always do not follow PRP (that is the sympathetic tone of heart).The workload of heart owing to spirit stress/when psychology stress change, the measured value that obtains according to the present invention was followed the tracks of the sympathetic tone of heart.Yet, (that is when, the sympathetic tone of heart) driving factors were the muscle power performance, then the sympathetic nerve of heart drove and changes incidentally at workload, but the measurement result that obtains according to the present invention as expected, (SA level) does not change incidentally.Therefore, in one aspect of the invention, the measurement result that obtains according to the present invention can be used for reflecting psychology stress level (that is, the level of WSS/DRS), and does not reflect the sympathetic tone of heart.It reflected really relate to psychology stress the time the sympathetic tone of heart, with reference to Figure 20,21,22 and 25 result of study.Result of study shown in Figure 20,21,22 and 25 is using 112 successively to suffer from another research of carrying out among angina pectoris (ischemic heart desease) patient who makes a definite diagnosis and confirmed that its result is illustrated among Figure 23 subsequently.Patient's group of test is correlated with, and surpasses the SA level that has rising among these patients of 90%.The β blocking medicine suppresses the conversion of beta-adrenergic sympathetic nerve sensor in the heart, thereby causes the tensile reduction of cardiac sympathetic nerve.The hypothesis of checking in this research is that the SA measured value between the patient of two subgroups (+/-β block treatment) does not change, and then support above-mentioned discovery, and the difference of tenderness aspect represents that SA is that cardiac sympathetic nerve is tensile and measures.In this research, in two subgroups of this colony, carry out the contrast of SA measurement level: 1) 62 patient and 36 patients that use β-blocade every day (last 14 patients do not obtain Useful Information) that do not use β-blocade.The result shows that between two groups of patients, the trial inspection of SA level does not have significant difference (p＞0.1).Therefore, this result has supported that the measured value (SA level) that obtains according to the present invention is measuring that psychology stress (=stress), and cardiac sympathetic nerve is tensile to be measured and be not only.
Yet method of the present invention also provide the alternative measuring method of heart working ability-, this need combine two measuring methods of the present invention, a method is used for " stress state ", another method is used for relaxation state:
Described method can be following mensuration experimenter's heart working ability: the method according to this invention is measured sympathetic tone respectively under stressed condition and at rest period, and based under stressed condition and determine experimenter's heart working ability in the mathematical combination of the sympathetic tone measured value of rest period.That described mathematical combination is selected from is poor, ratio and any monotonic function thereof.
In diabetics, the measurement result of glycosylated hemoglobin level is used to measure the long-term efficacy of antidiabetic treatment, but be recognized that this measurement provides about the information of the chronic stress level of diabetics (wherein numerical value raises relevant with the chronic rising of stress level).Yet, show, similar stress level the experimenter, the glycosylated hemoglobin of measuring is with of the present invention stress measured value relevant, thereby provide the method for the glycosylated hemoglobin level that is used for the indirect determination diabetics, measure sympathetic tone by the method according to this invention, and determine glycosylated hemoglobin level subsequently as the monotonic function of sympathetic tone measured value.
Thisly be determined at best results when pre-determining the experimenter and not being subjected to high-caliber chronic stress, for example by above-mentioned method or by the direct mensuration of glycosylated hemoglobin level.
This also for be used to prevent/reduce stress said method a variant is provided, that is, be used for diabetics.Described method comprise with at least one measured value of glycosylated hemoglobin consolidate stimulus threshold measured value (because the measured value of glycosylated hemoglobin can confirm that in fact the experimenter is subjected to high chronic stress level, mean be used to reduce stress intervention should have favourable effect.) can be in addition by research instantaneous stress measurement result (for example, above-mentioned PRP) confirms to intervene and be actually necessary, be subjected in the situation of chronic stress the experimenter, it is uncorrelated with measurement result of the present invention, and when having low-level chronic stress, between measurement result of the present invention and PRP, have intensive positive correlation.
Method of the present invention provides the possible self-monitoring of the variation in disease or the treatment process or self-monitoring plan, and these can be combined with rational the intervention:
Diabetes (DM) patient is measuring blood regularly, is used to estimate the requirement of insulin.Yet this need carry out blood test at present, and is that this always can not accomplish or practicable.Yet, utilize method and system of the present invention, for example wherein system is combined in the mobile phone, can allow DM patient in various situations, to follow the tracks of its blood glucose.Because compare the faster reduction of blood sugar level when stress level is high in the time of low with stress level, so of the present inventionly stress measuring method provide alternate measuring method, it can show compares more sugar of needs or more insulin with the dosage of expection.For example, DM patient can experience many stress the indication measurement value, the deviation of the delicate balance between its expression and insulin picked-up, Sugar intake and the accretion rate, and by with this system in siren (for example, mobile phone) the built-in computer that is connected, might receive about the suitable forecast of this deviation takes place, so that promote correct action process.
In addition, accepting chemotherapeutic cancer patient can be benefited from the therapeutical effect of optimizing.With above-mentioned consistent, a series of measuring methods of the present invention can provide stress level to be elevated to cause the chemotherapy effect reduces to a certain degree with the information of certain persistent period.Therefore, when providing this information by method of the present invention for the patient, described patient can select to take suitable action,, reduces stress level so that make treatment effectively action to greatest extent that is.Subsequently, fully whether the effectiveness of this action can be registered as-perfectly act on up to realization.
In addition, ischemic heart desease (IHD) patient can be provided by the similar information that is provided by moving recording that stress measured value.Described patient can know can cause strained physical conditions some day in the future, and has IHD can cause the circumscribed remarkable risk of determinant attribute.Use derives from the record and the continuous measurement value of a period of time before this incident takes place of system of the present invention, the patient can take correct action to guarantee constant low stress level (as measuring by method of the present invention), and it can make physical tasks be carried out and not be restricted.Yet in the process of incident, record can provide about whether needing the information of the action of other reduction sympathetic tone.This action can be for example Acupressure, rest or preventative antianginal drug.
Producing an important discovery of the present invention is that the method for mensuration sympathetic tone disclosed herein and/or stress level/WSS/DRS provides the objective evaluation of stress level.Therefore, might with described method with act on measure the experimenter stress the quality control of other method.
Think that now the application form of the stress level that is used to use measurement is valid and obtains utilizing in the whole world.Yet, have lastingly stress/patient's (such as female patient of for example suffering from breast carcinoma) of chronic stress in,-the inventor finds that the dependency in stress level of showing by inquiry to measure and blood between the stress hormone is minus, shows to have psychologic ignoring.Yet, have been found that technology of the present invention can measure this negative correlation, and provide thus application form is used for clinical objectively (with the Noninvasive) control that stress measure.This has obtained as previously mentioned the support of the test carried out 146 healthy people, and described test shows, what have in the people of high lasting stress level that half thinks that themselves is not subjected to stress or only being subjected to slight degree stress.In addition, whether to have the danger of possibility be to handle in brain under the situation of conscious perception not having in described stimulation.In addition, be used to check with respect to stress measurement result using the scientific research of application form to show, because 1) memory distortion, 2) influence and 3 of important experience) present stage stress twist and cause result's distortion.
Therefore, the present invention relates to be used for to determine whether the evaluation based on interview of stress level that the experimenter is carried out provides the method that stress indicate really, it comprises
A) when speaking face to face, utilize any method disclosed herein measure patient's sympathetic tone and/or stress level/WSS/DRS and
B) determine whether provide and the positively related result of the measurement result of step a based on the evaluation of interview, positive dependency is represented to provide real indication based on the evaluation of interview.
Therefore, said method allow correctly to design stress interview research.
With above-mentioned relevant, the inventor concludes, method of the present invention be used for monitoring in many cases stress/WSS/DRS easily with the method for Noninvasive.For example, method of the present invention can be used for monitoring experience may have development test that stress dependency character the experimenter stress level and/or stress character.Therefore, might check purpose be to reduce stress test of cure whether in fact have this effect, and might the confirmed test treatment whether show induce or reduce stress tendency, even in the purpose of treatment and the situation that stress have nothing to do.
Be used to control sympathetic tone/stress closed-loop process
The inventor is verified, psychology stress during the polymorphism receptor cell influence threshold of pain (Ballegaard S, Karpatschof, Nyboe J, W.Trojaborg, HansenAM, Magnusson G; Petersen BP. " Stress increases sensitivityof the biological warning system and defense reactions "; The manuscript that submission is used to announce).
This provides an embodiment of utilizing the closed circuit device of implanting of the present invention, and described closed circuit device is used to control sympathetic tone and/or stress level:
Little Intradermal or subcutaneous stimulating unit send the pulse (typically being electric pulse) of strength increase, and threshold of pain that can the polymorphism sensor that electricity physiology ground mensuration is adjacent when afferent nerve fiber is activated.Also can use with injure the reflection of retreating relevant spread out of motor neurocyte.In this case, measure the excitation threshold of these cells.
Excitation threshold is low and/or spread out of excitation threshold when low (rising of display psychology stress level) importing into, spread out of electricity irritation by the device initiation, thereby produce the outgoing signal that is sent to the central nervous system, the purpose of described signal is to regulate (=reduction) sympathetic activity level.
This closed circuit: 1) import pulse 2 into) handle the reaction 3 of paired pulses) spread out of pulse to change physiology's state and 4 of organism) to the effect that repeats to import into pulse control can with situation that lastingly stress be relevant in the most useful, for example metabolic syndrome, hypertension, depression, diabetes or ischemic heart desease.Other possible indication is various cancers and is the patient's condition of feature with the chronic pain.
The third part in above-mentioned loop has existed and really from known (the Sanderson JE of device of the epidural spinal cord stimulation that is used for the ischemic heart patient, Brooksby P, Waterhouse D, Palmer RBG, Neubauer K. " Epidural spinalelectrical stimulation for severe angina:a study of its effectson symptoms, exercise tolerance and degree of ischaemia " .Eur Heart J 1992; 13:628-633; De Jongste MJL, Haaksma J, Hautvast RWM, Hillege HL, Meyler PWJ, Stall MJ, Sanderson JE﹠amp; Lie KI.Effect of spinal cord stimulation on myocardialischemia during daily life in patients with severe coronaryartery disease " .Br Heart J 1994; 71:413-418; LandsherreCD, Mannheimer C, Habets A, Guilaume M, Bourgeois I, Augustinsson LE, Eliasson T, Lamotte D; Kulbertus H ﹠amp; Rigo P. " Effect of spinal cord stimulation on regional myocardialperfusion assessed by positron emission tomography " .Am JCardiol 1992; 69:1143-1149.
Therefore, an important embodiment of the present invention relates to the sympathetic tone level that is used to reduce the experimenter that these needs are arranged and/or the method for stress level and/or pain perception, and described method comprises:
A) stimulate experimenter's polymorphism receptor cell and/or spread out of motor neurocyte, so that measure excitation threshold, wherein preferred the stimulation is the form of electricity irritation;
B) monitoring in response to the stimulation of step a) from the polymorphism receptor cell and/or spread out of the pulse of importing into of motor neurocyte;
C) if the monitoring display excitation threshold in step b) reduces, this be psychology stress/ indication that WSS/DRS raises, stimulate efferent nerve fiber change the experimenter physiology's state and
D) repeating step a)-c).
The stimulation of the efferent nerve fiber in this embodiment of the present invention, preferred steps c) comprises peridural spinal cord stimulation.
Relevant embodiment is the closed circuit device that is used to control the stimulation of efferent nerve fiber, and it comprises
-be used for the polymorphism receptor cell and/or spread out of the equipment that motor neurocyte applies electricity irritation,
-be used to measure from the polymorphism receptor cell and/or spread out of the equipment that imports pulse into of motor neurocyte;
-be used for the equipment that pulse and standard value compare that imports into that will measure;
-be used for efferent nerve fiber is applied the equipment of electricity irritation; With
-be used for according to the equipment of relatively controlling the electricity irritation that efferent nerve fiber is applied that imports pulse and standard value into.
The progressive part of described new notion is:
-because stimulation sites, needs the extremely low intensive stimulation of importing near polymorphism neurocyte/spread out of motor neurocyte
-because identical, the intensity that need spread out of stimulation is low equally
-patient can relate to or not relate to by for example pressing button-this depend on step 2 be carry out automatically or help consciously to make the people show threshold of pain
-owing to stimulate and can often implement, can will stimulate required physiology's state adjustment to be reduced to floor level with respect to single.
Be used to measure stress/alternative method of sympathetic tone
Shown in embodiment 12, have been found that, by utilize on the health or the measured value of the intravital sympathetic tone subordinate point of body measure sympathetic tone/stress/method of WSS/DRS level and injury retreat reflection (NWR) relevant-in brief, the increase of stress level/sympathetic tone is attended by the increase of the existence of NWR.
This provides following probability, promptly, by measuring the approach (means) that animal is used as NWR in response to the existence of the injury retreatment reflection (NWR) that stimulates the stress level/sympathetic tone that raises in convenient and the fast measuring animal, described stimulation be have normal sympathetic tone or be not subjected to stress colony in most of individual animals in do not cause NWR, and cause the stimulation of NWR in the most of individual animals in the colony of sympathetic tone with rising or high stress level, wherein the NWR observed result in response to described stimulation is the indication that described animal has the sympathetic tone and/or the stress level of rising.
Described stimulation can be the stimulation of inducing mild pain, but also can be sensation verified great majority be subjected to stress animal in evoke NWR and great majority be not subjected to stress animal in do not evoke any stimulation (for example, observable or audible stimulation) of NWR.
Use the advantage of NWR (this is that the good performance that keeps takes place to go up in a kind system) to be, its can be for " animal of accepting to observe be in stress state? " problem qualitative fast answer is provided.The answer of this problem not only is correlated with when the research human experimenter, and when the research experiment animal, be correlated with equally, promptly, because the reliability that stress influence the scientific experiments that other animal is carried out in this laboratory animal-more briefly: wherein animal show in various degree stress/scientific research of WSS/DRS or sympathetic tone produces deviation probably between the result of different animals, its consequence is that this research needs more substantial animal prove any not same-action.This means, if might screen animal so as to get rid of by (seriously) stress those, then can reduce the number of animals that is used to study.In this case, can observe easily this animal whether exist NWR-this can by make regularly animal be exposed to mainly by stress animal in cause that the stimulation of NWR carries out.
Certainly, the human experimenter also can carry out " standardization " according to this principle, for example in the clinical trial or preclinical test situation that the measurement result of physiological role is relevant therein.Therefore, whether the human experimenter of the inferential NWR induction experiment of simplicity of design and observation post discussion reacts and the human experimenter who participates in scientific experimentation can be classified objectively NWR.
Similarly, might in animal of raising and train or farming animals, provide reliable animal welfare standard, and measure this animal in early days and be in stress state, even before their form the behavior of stress-induced.
The monitoring of NWR can be implemented with in the several different methods any.For the animal of particular type, can select NWR that is correlated with and the stimulation that can select to induce accordingly NWR.Behavior that then can monitor animal is for example by the photographing unit monitoring or by any other method easily of the NWR that observes animal continuously or regularly.
System of the present invention
The invention still further relates to the system of the sympathetic tone that is used to measure the animal that comprises the people, described system comprises:
A) memory device is used for being stored on the animal health or nociception calibration threshold value that the sympathetic tone neutral point of health is measured and store on the animal health or the nociception stimulus threshold of the sympathetic tone subordinate point in the health;
B) electronic circuit, described electronic circuit are programmed and are used for nociception calibration threshold value and nociception stimulus threshold are carried out date processing, so that obtain measured value.
In one embodiment, system of the present invention can comprise in addition that the body surface that is used for animal applies user's operating equipment of inducing inadequate stimulus and is applicable to storage because first user operates the memory device that the user of the nociception calibration threshold value of generation operates.
Perhaps, system of the present invention can comprise in addition that the body surface that is used for animal applies user's operating equipment of inducing inadequate stimulus and is applicable to storage because second user operates the memory device that the user of the nociception stimulus threshold of generation operates.
Describedly be used for applying the equipment that causes inadequate stimulus and can be included in first module, described electronic circuit can be included in another unit.In order to be implemented in the data necessary transmission between Unit first and second, described two unit can be equipped with the equipment that for example is used for radio communication.In so-called " distribution system ", first module can be for example portable unit that the user can easily carry, and another unit can be the central computer of doctor or hospital, and described computer is collected from the data that have portable unitary many different users separately.Randomly, described computer can be placed in user's the family.In distribution system, can advantageously mobile phone be used as communication equipment, be used for data are transferred to computer from portable unit, described portable unit is transferred to computer by for example conventional mobile telephone signal with data wireless.This signal can transfer to computer by the Internet by the mobile phone supplier.Randomly, Unit second can be formed by the mobile phone of programming, for example communicates by bluetooth TM and first module, and in this case, use utilizes the calculating of mobile phone and the system of storage device to replace distribution system.
In second embodiment, be used for applying the equipment and the described electronic circuit that cause uncomfortable stimulation and be integrated into same device.
In one embodiment, be used to apply the equipment that causes uncomfortable stimulation and be suitable for applying the stimulation that improves gradually, described memory device is applicable to that storage is operated with first user respectively and the corresponding irritation level of the moment of second user operation.
In one embodiment, the present invention relates to following system, uncomfortable stimulation comprises is exposed to Pressure stimulation, vibratory stimulation, thermostimulation, cold stimulation, electricity irritation, radiostimulation, chemical stimulation or its combination for causing of wherein applying.
In the particular of this system, the uncomfortable stimulation of inducing that is applied is stopped when first or second user operates.
The present invention relates in addition and is used to apply and measure stimulate so that measure the system of sympathetic tone, and described system comprises the sensing device of measuring unit and the stimulation of choosing wantonly that demonstration applied.
According to a specific embodiment of the present invention, described system comprises the label that is used for the labelling measurement point, makes described system to set up in the place that applies stimulation.
According to a specific embodiment of the present invention, described system equipment has the scale that is divided at least two zones, particularly is divided at least four zones, and described each zone is relevant with for example above-mentioned stress level 0,1,2 and 3.
According to a specific embodiment of the present invention, these zones can have different colors, pattern or other distinctive mark, make them to be distinguished from each other.
In one embodiment, described pressure is to apply by the pressure base (pressure base) or the mode of pressing plate
In a specific embodiment, the contact surface of pressure base is with resilience.
In other embodiments, described pressure base comprises liquid, gel and optional gas-filled bubbles.
In specific embodiment, the contact surface on the pressure base is less than 4cm
2, be preferably 1-2cm
2
Comprise according to the system of a specific embodiment of the present invention be suitable in the pressure base that applies external pressure on the health of animal with contact surface, be used to measure by pressure base at the pick off of applied pressure on the health, be suitable for storing respectively second pressure of first pressure of measurement and measurement and be suitable for calculating first pressure that expression measures and second pressure of measurement between the electronic circuit of readout of ratio, an embodiment of this system also comprises the sensing device that is used to show reading.If first pressure of measuring is the measurement of carrying out in the sympathetic tone neutral point, second pressure of measurement is the measurement of carrying out at sympathetic tone subordinate point, and then the level of activation of sympathetic nervous system can be used as readout and shows.
According to the system of a specific embodiment of the present invention comprise be suitable in second vibration force of the vibration base that applies external vibration power on the health of animal, the pick off that is used to measure the vibration force that is applying on the health by vibration base, first vibration force that is suitable for storing respectively measurement and measurement with vibration head and be suitable for calculating first vibration force that expression measures and second vibration force of measurement between the electronic circuit of readout of ratio, an embodiment of this system also comprises the sensing device that is used to show reading.If first vibration force of measuring is the measurement of carrying out in the sympathetic tone neutral point, second vibration force of measurement is the measurement of carrying out at sympathetic tone subordinate point, and then the level of activation of sympathetic nervous system can be used as readout and shows.
According to the system of a specific embodiment of the present invention comprise be suitable in second temperature of the heating base that applies heat on the health of animal, the pick off that is used to measure the temperature that is applying on the health by heating base, first temperature that is suitable for storing respectively measurement and measurement with contact surface and be suitable for calculating first temperature that expression measures and second temperature of measurement between the electronic circuit of readout of ratio, an embodiment of this system also comprises the sensing device that is used to show reading.If first temperature of measuring is the measurement of carrying out in the sympathetic tone neutral point, second temperature of measurement is the measurement of carrying out at sympathetic tone subordinate point, and then the level of activation of sympathetic nervous system can be used as readout and shows.
According to the system of a specific embodiment of the present invention comprise be suitable for apply the electronic pedestal with electrical header of external power on the health of animal, be used to measure second electric power of the pick off of the electric power that is applying on the health by electronic pedestal, first electric power that is suitable for storing respectively measurement and measurement and be suitable for calculating first electric power that expression measures and second electric power of measurement between the electronic circuit of readout of ratio, an embodiment of this system also comprises the sensing device that is used to show reading.If first electric power of measuring is the measurement of carrying out in the sympathetic tone neutral point, second electric power of measurement is the measurement of carrying out at sympathetic tone subordinate point, and then the level of activation of sympathetic nervous system can be used as readout and shows.
The contact surface of pressure base can be with resilience.As a result, obtained more accurate measurement, described contact surface is suitable for the uneven zone on the health and uniform pressure is provided.Therefore, described pressure is corresponding divided by the contact surface area with the power that applies.
Pressure base can comprise liquid, gel and optional gas-filled bubbles, thereby in the cooperation especially be close to of measurement point realization to body surface.
In an embodiment, can be towards the contact area of pressure base less than 4cm
2, for example be 1-2cm
2, perhaps less than 1cm
2, for example be 0.5-1cm
2
Pick off can comprise the force transducer of pressure drag.
Vibration base can comprise globular in fact or hemispheric vibration head.In some embodiments, the diameter of vibration head for example is 0.05mm-0.5mm less than 1cm, perhaps less than 0.5mm, for example is 1mm-4mm.
Wherein provide the embodiment of mechanical stimulus can comprise the magnetic actuator that is used to apply vibration force by the vibration force that applies.In some embodiments, described magnetic actuator can be arranged along the axle of wire, and the axle of described wire may be straight.Yet described axle can be a curve, perhaps for the human engineering shaping, for example is used for being engaged in user's hands.
Described magnetic actuator can comprise a plurality of slide units and slide bar.Each slide unit can comprise hole or chamber, so that allow it is arranged on the slide bar, thereby makes slide unit to slide along slide bar.Described slide unit and slide bar can be made by the nonmagnetic metal of for example aluminum.
Slide unit can be circular substantially shape, and each slide unit can comprise the groove of hoop on its outer surface.Provide described groove can be used to support the coiling of twining around described slide unit.Described coiling can be made by the magnetic metal of for example copper.
Described magnetic actuator can comprise a plurality of magnets and separator in addition, and described separator is made by the material with high magnetic permeability, can be unsaturated to guarantee them.
In some embodiments, slide bar has the hole or the chamber of longitudinal extension, and described magnet and separator alternately are arranged in the slide bar.Described slide bar can comprise two end fittings that magnet and separator remained on the appropriate location in the slide bar in addition.Described magnet can be in axial direction (parallel with pipe) magnetization, and can be arranged as and have alternative electrode direction.
Slide bar can be designed as in forming foraminous slide unit and moves, so slide bar and/or slide unit can scribble the material of reducing friction, for example lubricant.
Can produce and the vertical magnetic field of slide bar by magnet.Slide unit and slide bar can be set in the housing of ferrum, and the housing of described ferrum can further make the magnetic field maximization in coiling zone.
Described magnetic actuator can be connected in the control unit that can produce alternative current in coiling in addition.Described connection can or be passed through radio communication by lead.
Described magnetic actuator can produce vibration by the electric current in alternately winding the line.In a specific embodiment, can produce vibration with following method: the electric current in the coiling is in fact perpendicular to magnetic field, and its two be in fact in the vertical plane of axle with system.Produce power abreast with slide bar thus.Because for the magnetic direction of each slide unit is alternative and slide unit has alternative direction of winding, each slide unit/magnet forms the power of equidirectional to meeting.By changing sense of current, slide bar is shoved around.
In specific embodiment, the area of the contact surface of heating base is less than 4cm
2, for example be 1-2cm
2, perhaps less than 1cm
2, for example be 0.5-1cm
2
Described heating base can be included in the thermal actuator, and described thermal actuator can comprise control unit in addition.Described control unit can be positioned at the inside of thermal actuator, perhaps can optionally be connected with thermal actuator by wired or wireless connected system.
Can provide described control unit to be used for changing the temperature of contact surface.Can start measurement by the start button of pressing on the control unit.After reaching built-in initial temperature, can start measurement.In some embodiments, built-in initial temperature can be changed by the user.Preferred initial temperature is 35 ℃.Can contact surface when pressing, health automatically be started measurement the user.
Control unit can make the temperature of contact surface raise, and up to reaching built-in maximum temperature, perhaps moves up to the temperature that User break makes progress.When reaching user's the pain limit, the user can interrupt temperature upwards and move.Control unit can write down the temperature that interrupts when measuring.
Contact surface can cool off by natural cooling.In embodiment optionally, can be in thermal actuator built-in chiller.
Described electronic pedestal can comprise globular in fact or hemispheric electrical header.In some embodiments, the diameter of electrical header for example is 0.05mm-0.5mm less than 1cm, perhaps less than 0.5mm, for example is 1mm-4mm.
Wherein provide the embodiment of electricity irritation can comprise the electric actuator that is used to apply by applying electric power.These embodiments can comprise in addition can make electric current mobile control unit in electrical header.
In some embodiments, control unit can be converted into the electric current of alternating current the electric current of direct current, and vice versa.In embodiment optionally, can only use alternating current or unidirectional current.
In using galvanic embodiment, can provide control unit to change electric current in the electrical header.Can start measurement by the start button of pressing on the control unit.Control unit can comprise the built-in startup level of electric current.In some embodiments, described built-in startup level can be changed by the user.Can electrical header when pressing, health automatically be started measurement the user.
Control unit can make the DC current of electrical header increase, up to reaching built-in maximum current, perhaps up to the increase of User break electric current.When reaching user's the pain limit, the user can interrupt the increase of electric current.Control unit can write down the electric current that interrupts when measuring.
In the embodiment of using alternating current, can provide control unit to change the frequency of the alternating current in the electrical header.Can start measurement by the start button of pressing on the control unit.Control unit can comprise the built-in startup level of frequency.In some embodiments, described built-in startup level can be changed by the user.Can electrical header when pressing, health automatically be started measurement the user.
Control unit can make the AC current frequency of electrical header increase, up to reaching built-in maximum current, perhaps up to the increase of User break frequency.When reaching user's the pain limit, the user can interrupt the increase of electric current.Control unit can write down the frequency that interrupts when measuring.
In some embodiments, can be with alternating current and unidirectional current combination.
In some embodiments, electric actuator can be used to locate stimulation point in addition.
Described system can be incorporated in the device, and described device is preferably portable and provide power by one or more batteries.Thereby the user can carry this device at whilst on tour.
Sensing device can comprise electronic displays.
It is several discrete readouts that electronic circuit can be suitable for measuring readout, one (0,1,2,3) in 4 for example, the ratio of first measured value and second measured value is rounded off or be appointed as the discrete readout (0,1,2,3) that shows on sensing device.
Described discrete readout (0,1,2,3) can and first measured value and second measured value between ratio disproportionate.Therefore, described device can adapt to and lack proportionality or linearity between measurement result and sympathetic nervous system level of activation.Therefore, level 0 can be corresponding to second measured value, be first measured value 80% or bigger, level 1 can be the 55-80% of first measured value corresponding to second measured value, level 2 can be corresponding to second measured value, be that the 30-55% of first measured value and level 3 can be corresponding to second measured values, be first measured value 30% or littler.
Electronic circuit can be suitable for calculating first measured value as the average of a plurality of measured values, and calculates second measured value as the average of a plurality of measured values.Obtain the more reliable measurement result to people's stress level thus, the mistake that reduces the readout that causes owing to the measuring uncertainty in single measurement shows.
Fig. 5 represents system of the present invention, and for clear, described system is represented as and is incorporated in the same device.This device is for portable and comprise shell 10, electronic displays 8, control knob 9 and the pressure base 5 of stretching out from an end 7 of shell.The free end of described pressure base 5 has contact surface 6.In device, pressure base 5 is against force transducer that is connected in unshowned electronic circuit or pressure transducer 7.Electronic circuit can store by pick off 7 detected power or pressure measuring values.Described circuit can calculate in addition and readout is sent to electronic displays 8.Unshowned battery provides power for circuit.
In use, the user in its hands, hold device and and the sympathetic tone neutral point on the health applied the pressure that increases progressively, reach uncomfortable threshold value up to.Electronic circuit record by sensor to maximum pressure.The user presses control knob 9, then the sympathetic tone subordinate point on the health is applied the pressure that increases progressively, up to reaching uncomfortable threshold value.Electronic circuit record maximum pressure.When control knob 9 had been pressed, circuit calculated the readout of the ratio between expression first gaging pressure and second gaging pressure.In this embodiment, if second gaging pressure is respectively 80% or bigger, 55-80%, 30-55% or 30% or littler of first pressure, then readout is respectively 0,1,2 or 3.Described device can randomly be suitable for measuring the meansigma methods of a plurality of first pressure measuring values and the meansigma methods of a plurality of second pressure measuring values, measures readout on the basis of these meansigma methodss.Fig. 5 has shown one-shot measurement, and wherein the level of activation of sympathetic nervous system is 2, its corresponding to sympathetic tone subordinate point at 30% to 55% of the untimely pressure pressure that is the sympathetic tone neutral point.
Fig. 6 for example understands the details be used for contact surface 16 that human body is exerted pressure.Contact surface 16 comprises the soft relatively convex parts of being made by elastomeric material 18, and described elastomeric material is elastomeric material for example.The far-end that described parts 18 constitute as the device of system of the present invention.Soft relatively parts 18 are supported by hard relatively support unit 19, and described support unit 19 is by for example plastics or elastomeric material or steel is made and wherein limit the central protrusion that enters in the soft relatively parts 18.Therefore, the core of contact surface 16 is littler than the elasticity of its peripheral exterior section.Soft relatively parts 18 can guarantee that contact surface can make its shape adapt to the uneven surface of human body.On the other hand, hard relatively support unit 19 can guarantee that the power that is applied by the user is sent on the health rightly.Hard relatively support unit 19 by on the shell 20 that is installed in device or the pressure transducer 17 (for example, piezoelectric transducer) that is contained in the shell 20 support.
Although contact surface 16 is the columnar component with convex surface end portion in Fig. 6 illustrated, should be appreciated that, also considered alternate form.For example, it can be the cone with end portion of smooth or convex surface.
Should be appreciated that system of the present invention can comprise the equipment that is used for the animal body surface is applied other stimulation, the intensity of described other stimulation is lower than stimulus threshold, and for example being used for the treatment of and/or alleviating stress.For example, this equipment can be used as second independent pressure base and provides, and perhaps, they can be made of the pressure base that also is used for above-mentioned measurement purpose.Described first and second pressure base can be configured in portable unitary free end, for example form of a stroke or a combination of strokes unit.In one embodiment, optimum system choosing of the present invention therein includes only in the situation of a pressure base installation site, and first pressure base can be exchanged with second pressure base.In other embodiments, described system can hold first and second pressure base simultaneously, for example in portable unitary apparent surface's part, for example in two relative end.
The contact surface or the pressure base of device can be changed, so that allow user or doctor to select to be suitable for most the pressure base of specific purpose or particular patient.Can provide a plurality of pressure base in the element that provides with for example hand held device, described hand held device comprises the further feature of system of the present invention, for example pressure transducer, electronic control circuit, memory device and display.
Sound-producing device can be set come for the user provides acoustical signal, the indication the treatment or alleviate stress during apply required power.Perhaps, can provide optical signalling, vibration signal or other signal projector.Preferred generating means is connected in the electronic control circuit of reception from the device of the input of pressure transducer 7 or 17, so that the feature of sound can be different with the power that applies.For example, can change the persistent period at the reticent interval between sound level, frequency or the sound clip or the persistent period of fragment of sound.In one embodiment, the power that applies the user hour is not launched sound very much, and produces the sound with first feature (for example, producing the acoustical signal of low frequency) when the power that applies is suitable.If the power that applies surpasses predetermined threshold value level, the alarm signal of then launching high frequency.Consider other embodiment, be included in the embodiment that provides the embodiment of optical signal in the display of device or optical signal is provided by light emitting diode.
The embodiment of the mechanical stimulus of working pressure
The embodiment of device of the present invention is accommodated in (referring to Fig. 5) in the form of a stroke or a combination of strokes shell 4 and connects by the button 9 that starts on the described pen.Measure by the valve rubber of pushing on the end that is arranged on pen facing to patient's presser sensor point on one's body 5.Pen is not automatically closed when not carrying out other measurement in 1 minute.
After each measuring period, the COMPUTER CALCULATION stress factor, it is presented in the display 8.This demonstration is kept, up to starting next new measuring period or by the time restriction shutdown system.
Measuring principle and linearisation
Force transducer in the form of a stroke or a combination of strokes enclosure of system is pressure-sensitive ohmic resistor.When not having power, resistance is high relatively.Reduce for the force transducer resistance that increases progressively, the inverse of resistance is approximate proportional with power.
As shown in Figure 7, connect with fixed resister R1 on the pick off electricity, this series connection connects via the battery in the system.Therefore, the voltage of resistor R 1 is the function that acts on the power on the pick off.When power increased, this voltage raise, but its relation is not linear.
The maximum voltage of R1 is input to the analog input port of computer, in built-in AD-transducer, the voltage of measuring is converted into 0 to 1023 numeral.When cell voltage is used as the reference voltage of AD-transducer, measure the influence that can not be subjected to the variation of cell voltage.
Use following algorithm that the non-linear relation between power and the measured value is converted into the corresponding linear relation:
Corrected value=measured value * correction coefficient/(correction coefficient-measured value)
Correction coefficient is not scheduled to usually.Its numerical value determines during initial adjustment program.
The calculating of stress factor
Between the alignment epoch of system, store linearisation numerical value for 15kg power as the power reference value, be referred to as " reference value ".The linearisation numerical value of the power of the maximum during nearest measuring period is stored in the memorizer as variable, is called " maximum calibration value ".Then " maximum calibration value " is converted into the percentage ratio of reference load:
Maximum calibration value/the reference value of percentage ratio=100*
At last, the 7-segmented display shows the stress factor that is truncated to 2 decimals:
Show value=200-100*log
10(percentage ratio)
Be shown as figure among Fig. 8 as the stress factor of the function of " percentage ratio ".
Software configuration
The ultimate principle of date processing is referring to Fig. 9, and it has shown the flow chart of major function, and it should be quite clearly, need not to further specify.Not shown miscellaneous function, for example monitoring of cell voltage, pick off overload (generate during power＞15kg) beeping sound, or the like.
Processor cycles through major loop at a high speed continuously, hockets:
Date processing: collect analog data, with data conversion be digital numerical value, carry out mathematical calculation etc. and
Light in each sections of control light emitting diode indicator shows a numeral at every turn.
Only having an appointment of circulation time 20% is used for date processing.All the other times are used for the control of display.
Use the embodiment of the mechanical stimulus of vibration
The mechanical form of actuator is based on above-mentioned pressure actuator.Rubber closure is replaced with vibration head.The size of globular or hemispheric head is approximately 2mm.Amplitude and frequency that the control unit control based on microprocessor that connects is vibrated.
The mechanical part of actuator is presented in the sectional view of Figure 10.The part of projection is the aluminum wheel 30 that twines 0.1mm copper wire (not shown) in groove.There are eight this molectrons to be connected in parallel with alternative direction of winding.These are taken turns and are pushed to together, and forming internal diameter 6mm and length is the hole of 48mm.Just the aluminum pipe 32 that is fit to is set in described hole.In each end of pipe, end fitting 34 keeps content in position.Tube designs is can be inner mobile in the hole with the friction of minimum.Described pipe is filled with strong rare earth (neodymium) magnet 36 of being kept apart by little round iron dish 38.Magnet is arranged with axial direction (parallel with pipe) magnetization and with alternative polar orientation.
Described magnetic structure produces the magnetic field shown in Figure 11, has represented 5 magnets and 6 spacers.Preferably, spacer is to be made by the ferrum of high magnetic permeability basically, can be unsaturated to guarantee them.
As shown in figure 10, in coil with the pipe setting.Preferably, spacer is with respect to the wheel setting that centers.Any displacement all can weaken the pulling force that produces during by coil at electric current.Arrange eight wheels in iron-clad body (not shown), it further makes the magnetic field maximization in the coiling zone.Ideal state is, all magnetic field is perpendicular to the pipe in the coiling zone, because this power maximization that forms when electric current is flow through.Yet as shown in figure 11, in the actual enforcement of system, the fact is not like this.
The iron-clad body is made up of the cut plate 40 that piles up.Finish casing by end plate 41.The plate of aligned stack is ideally come in the little 2mm hole of using the utilization of steel pole (not shown) to cut in each plate.The ferrum cabinet arrangement is in the aluminum housing of extruding, and by the end piece shutoff device that is fit to.Each end of pipe is mounted with and is used for keeping pipe to be positioned at the spring at center with respect to wheel.
Consider fertility performance, the thickness of tube wall is minimized.From flux pattern (Figure 11) as seen, strong more near the local magnetic field of pipe more.Tube wall and make coiling away from the strongest zone, magnetic field at the wheel thickness of bottom portion of groove.
Preferred wheel and bar are formed by nonmagnetic substance basically.
Ideally, pipe and wheel should be made by non-conducting material.Alternating magnetic field produces eddy current and produce induced loss in aluminum.
Figure 12 has represented the different piece of actuator: the part 40 and 41 of aluminum wheel 30, aluminum pipe 32, end piece 34, rare-earth magnet 36, round iron dish 38 and iron-clad body.
Functional description
Electric current in the coiling is substantially perpendicular to magnetic field and its, and the two all is in the vertical plane of axle with device.Produce the power parallel thus with axle.Because for each magnetic direction of taking turns is alternative and wheel has an alternative direction of winding, each takes turns/and magnet forms the power of equidirectional to meeting.Actuator has limited stroke, because above-mentioned effect can shut down when pipe does not center with respect to coiling.
Actuator drives and software
Use simple H-bridger drive actuator, described bridger has the current chopping device (referring to Figure 13) of the steady-state current in the restriction coiling.Described FPGA comprises the uP system based on Altera NIOS, and it is equipped with the USB interface that is used to be connected in main frame.By changing sense of current, pipe is shoved around.
Adjust stroke by adjusting current limitation.This can influence the electric current in the coil, and influences the power that is applied on the pipe thus.Little of the program maintenance frequency of PC and the adjustment (referring to Figure 14) of stroke.Device connects as simple HID USB device and receives simple order by program.Vibration suspends after 10 seconds, in order to avoid make coil overheated.
According to a specific embodiment of the present invention, system can apply and measure thermostimulation, and described thermostimulation for example is a heat or cold.
The example of thermostimulation
The mechanical form of actuator is based on above-mentioned pressure actuator.Rubber closure replaces with the area of heating surface.The shape of the area of heating surface is identical substantially with the shape of pressure actuator.
Therefore, this embodiment comprises:
-comprise the form of a stroke or a combination of strokes shell of the hardware of system
-control chamber and
-battery charger.
This embodiment is included in the vertical metal knob of form of a stroke or a combination of strokes shell and at the button of lateral being called " heating ".Control chamber has luminous start button and two row display in lid.Described pen is connected in control chamber with thin cable.Control chamber comprises microprocessor, described microprocessor control temperature range and with respect to the temperature of time.
Start measurement by the start button of pressing on the control chamber.The button burn red is represented power connection, and the metal knob of pen is heated.Display shows: " add and pine for, wait for ".When pen reached start-up temperature (35 ℃) after several seconds, built-in acoustical generator was sent out beeping sound tout court, and display shows: " ready ".
The metal knob is pressed against at the sensitive spot on the patient body and by the button on starting writing " heating ".In case start button, the setting value of temperature raises gradually with invariable slope, reaches maximum temperature (45 ℃) at last.As the desired temperature of time function as shown in figure 15.Make the temperature following desired temperature of metal knob by the control loop in the software.During this period, show " in the measurement " on the display.
When the patient reaches its pain limit, should discharge the button on the pen and pen removed from skin.Red light in the start button on the control chamber is closed, and shows that the power supply of measuring in end and the pen is closed.
Control chamber calculates and shows then
Stress factor,
The experience Measuring Time and
The maximum temperature that reaches.
This demonstration is preserved, and up to starting new measurement, perhaps system reaches power supply turn-off time.When finish measuring period (light in the start button is closed), the temperature of metal knob is reduced by natural cooling.If started new startup before reaching start-up temperature, then this startup is delayed and the display demonstration: " in the cooling, waiting for ".When reaching start-up temperature once more, hear beeping sound, and show " ready " on the display.
Calculate the algorithm of stress factor
Stress factor is 0 to 100 numeral.Stress factor is the logarithmic function of the measurement time t of process.When this value is low, the stress factor height, vice versa.Calculate stress factor from following equation, wherein t is the Measuring Time of process, t
MaxAnd t
MinBe fixing but adjustable minimum and maximum time value:
If t＜t
MinStress factor=100
If t
Min≤ t≤t
MaxStress factor=100[log
10(t
Max)-log
10(t)]/[log
10(t
Max)-log
10(t
Min)]
If t＞t
MaxStress factor=0
Figure 16 represents the stress factor as the function of time.
Hardware designs
The simplified block diagram of hardware designs is presented among Figure 17.Shown in pen comprise Darlington power transistor Q1, resistor R 1 and be called the button of " heating ".Transistor have with pen on the thermo-contact of metal knob on.When being pressed, button sends the heating order to CPU.Q1 has two functions.In each sampling period, continue 10 milliseconds, play the effect of temperature sensor in 2 milliseconds of its pro-.In 8 milliseconds first subsequently, it plays the effect of heating element heater.This is illustrated in the sequential chart of Figure 18.
In 2 milliseconds of Measuring Time that take place subsequently, with reference to the sketch of Figure 17: be placed in the effect that Darlington transistor Q2 in the control chamber plays the switch of the collector current of closing Q1.By resistor R 2, little electric current (several milliamperes) flows through Q1 base-emitter-diode (Q1basis-emitter-diodes) and resistor R 1 arrives ground wire.Voltage on the some A is only by the voltage drop V by base-emitter-diode
BeDecision, described voltage drop is temperature-dependent.When room temperature, V
BeBe about 1.4V, this voltage reduces with 4mV/ ℃ ratio approx with the rising of temperature.Direct current amplifier will be put the voltage amplification of A, provide corresponding to 15-75 ℃ 0
5V output.10 bit A/D converters among the CPU receive this voltage and are the numeral of 0-1023 with temperature inversion in software.
In the heating cycle of max8 millisecond, below the generation: Darlington transistor Q2 works as electrical switch and connects, and it is controlled by CPU.The voltage at some B place is near cell voltage V
BAT=14V.The voltage of point A is near 2.1V, because it is that described R2 and diode D1-D3 have the knee voltage of 0.7V separately by the potentiometer decision that comprises R2 and diode D1-D3 now).Because base-emitter voltage V
BeBe about 1.4V, and R1=1 Ω, so the collector current IC among the Q1 is
I
C＝(V
A-V
be)/R1＝(2.1-1.4)/1＝0.7A
Under this electric current, the power of sending among the Q1 is
P≈V
BAT·I
C＝14V·0.7A＝9.8W
Make Q1 raise rapidly with the temperature of the metal knob that is connected.
As shown in figure 18, this power is only sent in 8 milliseconds first.The width Delta t of output pulses regulates by the ratio control circuit based on software by CPU:
Δ t=K (T
The set-point-T
Measured value)
Wherein K is adjustable gain constant, T
The set-pointBe the temperature of setting, T
Measured valueBe observed temperature.
Display is the 16 bit digital matrix displays that duplicate rows shows, has built-in controller and backlight, by 14 circuit controls from CPU.At not shown 5 buttons of Figure 17, described button is arranged on control chamber inside and all is connected in CPU.These buttons of called after Reset (replacement), Mode (pattern), Up (making progress), Down (downwards) and Save (preservation) can be used for resetting of CPU and adjust following parameter: T respectively
Start, T
Max, slope, t
Min, t
Max, and the gain K.
Power supply is by the rechargeable Li ion battery supply of built-in 14V.When start button is pressed, hardware based control logic energized, also the remainder for CPU and circuit provides 5V.In the past 3 minutes and without any the action situation under, CPU sends power disconnect signal to power control circuit.
Battery charger is the commercially available unit by network supply.When charging, connect in control chamber with cable.Because safety, when the plug of charging cable was inserted into control chamber, electronic equipment was separated from battery.
Software
Software configuration is that so-called " Finite State Machine (finite-state automaton) " is the structure of a kind of PLC of being generally used for (programmable logic controller (PLC)).This structure comprises the closed circuit of a plurality of states, and each state comprises one or more actions and a transformation.Pointer only starts a kind of action of state in the operation of whole loop high speed.This startup continues many successive operations, to the last realizes being subordinate to the condition (very) of transformation (belonging transition).In service subsequently starts another kind of state.
The condition that changes is: timer time to (Timer run-outs), enumerator reach some numeral, from the signal of the other parts of circuit be set or reset, button is pressed or release etc.(other explanation is especially referring to " wikipedia.org ").
The example of electricity irritation
Electricity irritation can provide by utilizing alternating current and/or unidirectional current.For example, can use commercially available actuator: derive from MibiTech ApS, the Tao of Denmark, referring to WO2004/062723, it is merged in this paper as a reference.The head of this electric actuator is globular basically or spheric, and diameter is about 2mm.This electric actuator provides electricity irritation by the alternating current that applies.
Electric actuator has two functions: 1) actuator can be used for locating the exact position and 2 of stimulation) actuator can be used for carry stimulating.That is to say, raise, then can make sympathetic tone subordinate point in a period of time, accept the electricity irritation that intensity is lower than stimulus threshold if the measured value of sympathetic tone and/or stress level shows sympathetic tone and/or stress level.
The advantage of this electric actuator is to locate stimulation point well.
This electric actuator is described to have the electronic therapy device of first and second electrodes or probe, is used to electrically contact individual health.This device has and is used to electrode that the voltage supply equipment of ac output voltage is provided, be used to make alternating current to pass through individual health, and this voltage supply device is suitable for controlling the frequency of output voltage, makes output voltage frequency in time automatically change between low frequency and high frequency.The voltage supply equipment can be suitable for controlling the frequency of output voltage, so that output voltage frequency changes between low frequency and high frequency with the interval of rule.This actuator is described among the WO 2004/062723 " Electro-therapeutic device andmethod of electro-therapeutic threatment " (MibiTech ApS) in addition, and described WO 2004/062723 is merged in this paper as a reference.
According to a specific embodiment of the present invention, described system can apply and measuring radiation by for example laser instrument, light emitting diode, infrared light supply, ultraviolet source and/or white light source, for example infrared ray, visible light and/or ultraviolet or its combination spectrum.
According to a specific embodiment of the present invention, described system can apply and measure chemical stimulation, and described chemical stimulation for example is organic compound or inorganic compound.
The present invention relates to the purposes that the system that applies and measure stimulation is used to measure sympathetic tone in addition, may further comprise the steps: measure the stimulation that applies with stimulus threshold in one or more sympathetic tone neutral points and measure the stimulation that applies with identical stimulus threshold at one or more sympathetic tone subordinate points.
According to a specific embodiment of the present invention, using system applies and measures the stimulation that is used to measure sympathetic tone, measures to be in the front of clavicle upside and/or to carry out in the back on corresponding to the spinal column of TH 10-11 in the stimulation that one or more sympathetic tone neutral points apply with stimulus threshold.
In one embodiment, the system that the present invention relates to be used to apply and measure stimulation is used to measure the purposes of sympathetic tone, the measurement of the stimulation that applies with stimulus threshold at one or more sympathetic tone subordinate points is on innervation ground (promptly, distribute relevant with nerve) carry out to the one or more positions on the innerv skin of heart corresponding to sympathetic nervous system, for example carry out at the one or more points that are included in in the lower area: at the intermediary C.V.17 of breastbone, ST 18 and the Per between nipple and anterior axillary fold 1 between inframammillary two ribs; And carry out on the back of TH 3-6 corresponding to zone between the omoplate, wherein select the pain spot of described point.
According to a specific embodiment of the present invention, use can apply with measurement mechanical stimulates for example system of pressure.
According to a specific embodiment of the present invention, use can apply with measurement mechanical stimulates for example system of vibration.
According to a specific embodiment of the present invention, use can apply and measure thermostimulation for example heat or cold system.
According to a specific embodiment of the present invention, use can apply and measure electricity irritation for example alternating current or galvanic system.
According to a specific embodiment of the present invention, use can apply the system with measuring radiation, described radiation is infrared ray, visible light and/or ultraviolet or its combination spectrum for example, and described system provides with for example form of laser instrument, light emitting diode, infrared light supply, ultraviolet source and/or white light source.
According to a specific embodiment of the present invention, use can apply and measure for example system of organic compound or inorganic compound of chemical stimulation.
In aspect other, the invention provides the mobile phone that comprises or be connected in an embodiment of system of the present invention.Described system can fully be incorporated in the mobile phone, therefore comprises causing uncomfortable equipment and reading device in phone.Perhaps, can a part be incorporated in the phone system.For example, can will cause uncomfortable equipment be included in the shell of mobile phone, and reading device can be arranged on So Far Away, provides suitable equipment to accept data from phone in this place.In one embodiment, can provide computer system, for it transmits the numerical value of reading of expression threshold of pain, stress factor or other numerical value in hospital or Doctor's office.This computer system also can be arranged in the patient family.Reading device can be connected in the display of mobile phone, and/or is connected in the microphone of the phone that can send suitable sound signal (for example, artificial voice signal).For example, critical stress factor can be shown as the warning on the display, perhaps can be shown as the alarm signal of acoustics.
Mobile phone goes for reminding the user of phone to carry out the threshold of pain measurement.For example, phone can be programmed at given time point and send alerting signal, perhaps it can be programmed for and send alerting signal when receiving predetermined radio signal (for example being included in SMS or the MMS information).Thus, doctor or other people can point out the user of mobile phone to carry out the nociception stimulation by the system of the present invention that is incorporated in the phone.
Phone can be programmed for the measurement that record is carried out by the user, promptly stores the numerical value of measuring several times, comprises nociception stimulus threshold for example, stress factor or other numerical value that can be produced by system of the present invention.Similarly can write down the time of measurement.This record can also carry out in the equipment a long way off, and phone can be by radio communication and the contact of described equipment.Perhaps, can work as phone near computer system the time by wired or wireless contact (bluetooth for example
TM) data that deposit in are sent to computer system from phone.
The startup that is incorporated in the equipment that causes stimulation in the phone can be by telephone keypad, by touch screen, carry out by voice recognition or by the independent button that is designed for this purpose.
Further specify the present invention by following examples.
Embodiment
In all embodiment, by manometry institute applied pressure the time, the unit of all measured values all is pound (lbs)/cm
2, be expressed as lbs hereinafter.
In an embodiment, when the pressure of measuring that finger applies in the pressure sensibility threshold value, the unit representation of all measured values is: 0 ,+, ++, +++, wherein 0 expression is with the threshold value applied pressure of pressure sensibility, wherein=,+, ++, +++point applied pressure at sympathetic tone subordinate point with identical pressure sensibility threshold value usefulness, wherein 0 equals at sympathetic tone neutral point applied pressure, and+, ++, +++expression applied pressure is relatively low.
Embodiment 1a
Measure people's sympathetic tone by the following method: in front in the sympathetic tone neutral point gaging pressure sensitivity threshold value of clavicle upside, measuring institute's applied pressure is 13.8lbs by piezometer.Then at sympathetic tone subordinate point C.V.17 with identical pressure sensibility threshold measurement applied pressure, be 13.0lbs.Thus, in the threshold value of identical pressure sensibility, be at 94% of sympathetic tone neutral point institute applied pressure at sympathetic tone subordinate point institute applied pressure.According to the present invention, this stress corresponding to level 0.Fill in application form by this people then about its stress level, described application form confirm this people do not demonstrate clinical stress sign.
Embodiment 1b
Measure another person's sympathetic tone according to following method.In front in the sympathetic tone neutral point gaging pressure sensitivity threshold value of clavicle upside, measuring institute's applied pressure is 14.3lbs by piezometer.Then at sympathetic tone subordinate point C.V.17 at identical pressure sensibility threshold measurement applied pressure, be 11.0lbs.Thus, in the threshold value of identical pressure sensibility, be at 77% of sympathetic tone neutral point institute applied pressure at sympathetic tone subordinate point institute applied pressure.According to the present invention, this stress corresponding to level 1.
Embodiment 1c
Measure the 3rd people's sympathetic tone according to following method.In front in the sympathetic tone neutral point gaging pressure sensitivity threshold value of clavicle upside, measuring institute's applied pressure is 10.0lbs by piezometer.Then at sympathetic tone subordinate point Per 1 at identical pressure sensibility threshold measurement applied pressure, be 7.0lbs.Thus, in the threshold value of identical pressure sensibility, be at 70% of sympathetic tone neutral point institute applied pressure at sympathetic tone subordinate point institute applied pressure.According to the present invention, this stress corresponding to level 1.
Embodiment 1d
Measure the 4th people's sympathetic tone by the following method: by piezometer in the back on spinal column corresponding to the sympathetic tone neutral point gaging pressure sensitivity threshold value of TH-10-11, measuring institute's applied pressure is 24.0lbs.In identical pressure sensibility threshold value, measure in the back that the sympathetic tone subordinate point applied pressure corresponding to TH 3-6 is 22.5 pounds on spinal column.In identical pressure sensibility threshold value, be at 94% of sympathetic tone neutral point institute applied pressure thus at sympathetic tone subordinate point institute applied pressure.According to the present invention, this stress corresponding to level 0.Fill in application form by this people then about its stress level, described application form confirm this people do not demonstrate clinical stress sign.
Embodiment 2a
Measure people's sympathetic tone by the following method: in front in the sympathetic tone neutral point gaging pressure sensitivity threshold value of clavicle upside, measuring institute's applied pressure is 17lbs by piezometer.Be 8.0lbs at sympathetic tone subordinate point C.V.17 at identical pressure sensibility threshold measurement applied pressure then.Thus, in the threshold value of identical pressure sensibility, be at 47% of sympathetic tone neutral point institute applied pressure at sympathetic tone subordinate point institute applied pressure.According to the present invention, this stress corresponding to level 2.
Embodiment 2b
Measure another person's sympathetic tone according to following method.In front in the sympathetic tone neutral point gaging pressure sensitivity threshold value of clavicle upside, measuring institute's applied pressure is 10.5lbs by piezometer.Be 5.0lbs at identical pressure sensibility threshold measurement to institute's applied pressure at sympathetic tone subordinate point St.18 then.In identical pressure sensibility threshold value, be at 48% of sympathetic tone neutral point institute applied pressure thus at sympathetic tone subordinate point institute applied pressure.According to the present invention, this stress corresponding to level 2.
Embodiment 2c
Measure another person's sympathetic tone according to following method.In front in the sympathetic tone neutral point gaging pressure sensitivity threshold value of clavicle upside, measuring institute's applied pressure is 14.0lbs by piezometer.Exerting pressure in the institute that sympathetic tone subordinate point Per 1 measures in identical pressure sensibility threshold value then is 5.0, and the exert pressure of measuring at sympathetic tone subordinate point St.18 is 5.5lbs.In identical pressure sensibility threshold value, be respectively at 36% and 39% of sympathetic tone neutral point institute applied pressure thus at sympathetic tone subordinate point institute applied pressure.According to the present invention, this stress corresponding to level 2.
Measure people's sympathetic tone by the following method: in front in the sympathetic tone neutral point gaging pressure sensitivity threshold value of clavicle upside, measuring institute's applied pressure is 9.0lbs by piezometer.Be 2.0lbs at sympathetic tone subordinate point C.V.17 at identical pressure sensibility threshold measurement applied pressure then.Thus, in the threshold value of identical pressure sensibility, be at 22% of sympathetic tone neutral point institute applied pressure at sympathetic tone subordinate point institute applied pressure.According to the present invention, this stress corresponding to level 3.
The people who mentions in embodiment 3 accepts the system of the present invention at individual's calibration, be used to measure the required institute's applied pressure of decision sympathetic tone, described system comprises measuring device and scale (scale), in this embodiment, it is divided into four zones corresponding to four stress levels, and described system shows institute's applied pressure and is provided with the label that is used for the one or more measurement points of labelling.By the system of the present invention that use provides, this people can what its sympathetic tone of timing easily in office.Thereby subsequently, corresponding with the pressure sensibility threshold value of sympathetic tone subordinate point in which zone by observing applied pressure, this people can measure its sympathetic tone.A zone is corresponding to 30% (level 3) that is lower than at the pressure sensibility threshold value institute applied pressure of sympathetic tone neutral point; Another zone is arrived less than 55% (level 2) corresponding to 30%; The 3rd zone is arrived less than 80% corresponding to 55%; The 4th zone is corresponding to more than or equal to 80%.
Measure people's sympathetic tone by the following method: in front in the sympathetic tone neutral point gaging pressure sensitivity threshold value of clavicle upside, measuring institute's applied pressure is 9.0lbs by piezometer.Be 2.0lbs at sympathetic tone subordinate point C.V.17 at identical pressure sensibility threshold measurement applied pressure then.Thus, in the threshold value of identical pressure sensibility, be at 22% of sympathetic tone neutral point institute applied pressure at sympathetic tone subordinate point institute applied pressure.According to the present invention, this stress corresponding to level 3.Fill in application form by this people then about its stress level, described application form show this people demonstrate chronic accumulation stress symptom.
Use the pressure sensibility threshold value of finger mensuration to be " +++".
All around, after carrying out suitable intervention, this people is repeated identical measurement.
In front in the sympathetic tone neutral point gaging pressure sensitivity threshold value of clavicle upside, measuring institute's applied pressure is 10.0lbs by piezometer.Be 9.5lbs at sympathetic tone subordinate point C.V.17 at identical pressure sensibility threshold measurement applied pressure then.Thus, in the threshold value of identical pressure sensibility, be at 95% of sympathetic tone neutral point institute applied pressure at sympathetic tone subordinate point institute applied pressure.According to the present invention, this stress corresponding to level 0.The pressure sensibility threshold value of using finger to measure is " 0 ".
Simultaneously, this people report, in the past record stress clinical symptoms disappeared.
In the tests of using 250 people that select at random to carry out, the examination physiological stress and clinical stress between dependency.Described 250 people that select at random are required to fill out a questionnaire, and whether have experienced some special situation to determine them around nearest.Always have 35 problems, its represented all different stress clinical indication.
Then, instruct these people by at first discerning the clavicle upside, and record obtain the pressure sensibility threshold value and need apply what kind of intensity of pressure there, comes themselves is checked.With this as starting point, instruct these people find out C.V.17 and based on determine to obtain the identical required relative applied pressure of pressure sensibility threshold value for the used same procedure of clavicle upside, carry out with 4 scales: 0 ,+, ++, +++.
Collect all application forms then and analyze.
The dependency that obtains on respect to C.V.17 between the threshold value institute applied pressure at the clavicle upside is significant (p＜0.001), promptly the symptoms of stress in nearest individual experience all around is many more, then, more little at the thorax institute applied pressure of a C.V.17 with respect at the clavicle upside.
Embodiment 7 (the prognosis purposes of method/system)
Fully healthy people (for example musician or commander) uses described method and system to guarantee low measured value every morning, has provided to its prognosis the optimum utilization of its resource when playing subsequently or commanding in this day.
If at the measured value height in a morning, then this measured value allow to start reduce stress activity, for example take exercise/loosen.After finishing activity, this people can measure this activity and whether obtain effect of sufficient, promptly obtains low measured value.If do not meet the desired target, can repeat described process.
Embodiment 8 (daily stimulation) with preventive effect
With the same in embodiment 7, yet the system among this embodiment also is used to carry out following action:
By described system, keep intensive continuous pressure at sympathetic tone subordinate point, make described pressure be felt but described stimulation does not cause pain.After second, the pain that the people writes down the below reduces at 20-40.
By described system, this can be recorded as 50% threshold of pain that raises; Can make threshold of pain be elevated to 60% thus from 40% of the threshold value of sympathetic tone neutral point.
On the physiology, this is equivalent to pass through " stress stage " and starts the recovery stage.
This action can help prevention to bear stress.
Embodiment 9 (be used for instant-free stress special stimulation)
With the same among the embodiment 7, yet in this embodiment, numerical value that user record is high and execution immediately are as embodiment 8 described actions.After correctly carrying out described action, the user can write down 50% the improvement of may reaching of measured value at 20-40 after second.
The measurement of embodiment 10 study
Because described method and system provides stress level (promptly, the activity of sympathetic nervous system) measurement at once, the people can know its " value in morning " and repeat described measurement in this sky, so that determine to influence the particular case (for example, talk, order, phone information, task) of stress level.
Because stress stage started in several seconds and disappears in second at 20-40, described method and system provides and has been used to how learn different even in everyday situations (with positive and passive direction) influences the brand-new probability of stress level.
In the long term, described thus method can tell whether this people has for example obtained the relaxation effect of expectation vacation.
Embodiment 11 (the present invention is used for determining the purposes of warning system biology state)
Foreword-warning system biology and warning system sensitivity
Warning and system of defense have been the basic part of living organism surviving policy in whole evolutionary process.Early stage what evolve, antibacterial such as escherichia coli have formed special sensory system based on the molecule on the bacterium surface, and its monitoring is the chemical condition-and formed the regulating system that may be used to induce stress tolerance of the environment aspect the various factors of key in the existence for them.In addition, the most primary neural reflex has been represented in the reflection (a kind of retreatment reflection) of curling of lancelet (vertebrate early stage ancestors).
In animal, formed the ability of the histoclastic environmental stimulus of detection possibility that is called as the nociception system in addition, it makes the needed information of optimal response for organism provides to the hostile environment condition, and may also be attended by reflex response and for example retreat.The nociception system is based on polymodal receptor, and described polymodal receptor is a kind of from the fish to the level vertebrate animals and people's undifferentiated neurocyte of having same nature in interior evolution chain from start to finish.Sensor is subjected to mechanical pressure, temperature and tart stimulation.The sensitivity of sensor can experience various adjustings:
An aspect is the analgesia of stress-induced, and the pain sensation is suppressed therein.This help injured/suppress the general pain sensation the animal of fight, so that optimize its fight/ability of runing away.Second aspect is the hyperpathia of stress-induced, and the pain sensation raises therein.This flicks sensitivity in the test at pawl pressure test and afterbody respectively and raises and observe in animal.Cardiac's (in heart patients) clinical observation result shows that it is relevant with the tenderness rising of particular acupoint that the level of sympathetic tone raises, and other point on the body surface is unaffected.Similarly, the tenderness that relates to these acupuncture points of lower sympathetic tone level reduces.
Unpub by the inventor in the exploratory study that implement, that in 250 healthy people, carry out, with non-acupuncture point and stress the degree of self-report when comparing, between the self-palpation degree of the tenderness of particular acupoint, found significant dependency.This observed result is not described to the part of animal and/or people's warning system at present as yet.From the viewpoint of teleology and evolution, all by using a kind of mechanism to improve the existence potentiality, this is proved when can trace back to fish in the evolution process in two aspects stress regulating of nociception.
Therefore, the inventor recognizes that in rugged environment, the sensitivity of the polymodal receptor in the heart in the segmental innervations raises, and sympathetic activity raises simultaneously.This warning system sensitivity (WSS) can be by described device and system are measured herein.
As instantaneous stress the serum cortisol of measuring
Several studies show that, serum cortisol or saliva hydrocortisone may be useful instantaneous stress indicant.Coming among the patient of city emergency unit owing to cardiopulmonary arrest, the serum cortisol level raise during preceding 6 hours that recover after major cycle significantly, and reduced significantly in 18 hours processes subsequently.At the philtrum of experience coronary bypass transplanting (CABG), find that serum cortisol raises after operation.Have been found that serum cortisol measured value in 24 hours can be used for understanding the reaction to apoplexy, the serum cortisol level is high more, then the deficiency on the neurological is serious more, observes bigger ischemic lesions on CT, and produces worse prognosis (p＜0.05).
In the people of short-term or chronic unemployment, the reduction of health performance is relevant with the emotionally disturbed increase with the serum cortisol rising, and described emotionally disturbed obtains from the application form evaluation.In the soldier, find between serum cortisol and acute stress, to be positive correlation.In fish, have been found that serum cortisol raises during being exposed to acute stress.Yet, this be reflected at fish be exposed to lastingly stress the time do not exist.
In the female patient of breast carcinoma, compare with the matched group of not receiving treatment in early days, cognitive behavior stress governing plan reduce the serum cortisol level.In the women of primary breast cancer, carried out anecdotal exploratory study, 6 months observation period, find comprehensively stress governing plan to reduce median blood pressure (middle blood pressure), reduce lastingly stress the clinical indication number, reduce the stress level of self evaluation and reduce tenderness degree on the chest ad-hoc location.Yet glycosylated hemoglobin and serum cortisol all do not change.
As instantaneous stress pressure-speed of measuring-product (PRP)
In cardiology, pressure-speed-product (PRP) conduct is used for the index of a practicality of myocardium oxygen picked-up, and reflects the heart running thus.Therefore it, be the label that is fit to of cardiac sympathetic nerve tension force transient change mainly by the control of beta-adrenergic catecholamine.
Glycosylated hemoglobin as lastingly stress measure
Several studies show that, glycosylated Hb H bA1c can be used as lastingly stress measure.In the internal medicine student, compare with other student, have been found that HbA1c raises before examination.In addition, in the examination group, after 4 months, HbA1c significantly reduces.These results obtain proof subsequently in other research.In the Australian people of locality, compare with the Australian in west, the HbA1c that find to raise as locals " westernization (westernization) " lastingly stress possible sign.In the patient of myocardial infarction and non-diabetic, the Hb1Ac when access is relevant with 5.5 annual survival rates significantly with serum cortisol.Have been found that in Japan and Denmark workman persistent work strain all relates to the Hb1Ac level and raises.Compare with matched group, in beaten women, find higher levels of HbA1c.About stress the summary of physical measurement in, Kelly and Hertzman recommend strongly HbA1c can be used as lastingly stress measure.
Blood pressure as lastingly stress measure
Stress be the intensive paathogenic factor of metabolic syndrome lastingly.It is relevant with obesity, insulin resistance, hypertension and dyslipidaemia to influence 4,000 ten thousand American metabolic syndromes, and these all are the risk factors of cardiovascular disease and premature death.Thought blood pressure with the increase at age raise with lastingly stress be relevant.
Instantaneous stress during, systolic pressure more promptly changes than diastolic pressure.In the women of primary breast cancer, carried out anecdotal exploratory study, 6 months observation period, find comprehensively stress governing plan to reduce median blood pressure (middle blood pressure), reduce lastingly stress clinical indication number, the stress level and the warning system sensitivity of self evaluation.Yet glycosylated hemoglobin and serum cortisol all do not change significantly.
Follow lastingly stress stress weaken
In being exposed to the fish of environmental pollution, observed the hydrocortisone stress that weakens.In rat, have been found that maternal deprivation produces the lasting unusual of the behavior of Hippocampus and neuroendocrine function, Hippocampus is an important area relevant with stress in the brain.Have been found that the mother who reduces the people who measures as natality or infant weight stress influence subsequently stress in life, and significant sex difference is arranged.Two research all proved be exposed to lastingly stress the people of others health to the cardiovascular that the weakens response of acute stress.
In the unpub exploratory study that the opera singer is carried out, the inventor observes, lastingly stress be low when (measure into HbA1c level low or normal), find dependency at WSS after performance and PRP before the performance between changing, and lastingly stress degree height (measuring high HbA1c level) time, can not observe this dependency.
The inventor finds, with performance or spirit stress test relevant stress during, stress reduce relevant (referring to Figure 28-30) with motility lastingly
Be used to reduce controlling of warning system sensitivity (WSS)/defense reaction/reflex sensitivity (DRS)
The selection for the treatment of
From clinical viewpoint, measure WSS/DRS and only when its positive impact that can be subjected to moving consciously, be only significant as the ability that stress measure.The unpub clinical exploratory study that in Denmark and acupuncture Japan clinic 183 successive patients is carried out shows, after acupuncture 3 minutes, and the reduction of 94% patient experience WSS, median act as 35% reduction.Still can not determine to have the intervention of other kind of similar reaction and effect ratio.Therefore, because the purpose of present embodiment is to confirm that the warning system sensitivity of measuring by method and apparatus of the present invention raises and can be weakened, it is first to select that the results suggest of described exploratory study is used acupuncture and moxibustion treatment.In other research of former announcement, have been found that acupuncture increases pressure-speed-product (PRP) of cardiac and regulates healthy people's PRP.
The design of investigational studies 1
The original purpose of research 1 is to confirm discovery of the present invention, promptly, when instantaneous stress level is identical, with physiognomy ratio with low HbA1c level, people with high glycosylated hemoglobin (HbA1c) serum levels shows warning system sensitivity (WSS) and raises, and it is to measure by the tenderness degree increase of the inventive method as the specified point of skin that described warning system sensitivity (WSS) raises.
Second purpose of this research is to probe into following hypothesis:
A. with the physiognomy ratio with low median blood pressure (MBP), the people with high median blood pressure (MBP) has high WSS.
B. with the physiognomy ratio with low PRP, the people with high PRP has high WSS.
This test is open, prospective observational study.
The participant who enlists enlists from private corporation and by the invitation of medium.300 whole people comprise following condition: have the people of high stress level of expection and the people with the low stress level of expection.Comprise that the age is the 18-75 masculinity and femininity in year.
Exclusion standard: the women of diabetes (insulin-dependent and non-insulin-dependent), psychiatric disorders, anemia of pregnant woman and suckling, at nearest 6 months with crossing the general steroid medicine, measuring WSS in the past.
Being selected to be based on of experimenter comprises the group that can reflect general healthy adult colony.
Use following program:
■ provides verbal and written data for the experimenter before by phone and mail/electronic mail access.
■ signs Informed Consent Form
The ■ raw data
Before base line measurement, fill out a questionnaire, so that the exclude filter failure.All data are collected with the form of printing.All transfer of data are analyzed afterwards to the SPSS data base.Use screening and registration daily record.
Research is carried out in the place of company or at the inventor's acupuncture center.
The individual actuation variable of measuring is as follows:
Application form
The ■ demographic statistics; The self-perception of age, sex, BMI, waistline, concomitant disease, the medicine of following, stress level
Physiologic measurement
■ measures glycosylated hemoglobin (HbA1c) from capillary blood; That is, get blood from experimenter's finger tip.With its as lastingly stress measure.
■ is by automatic monitoring record blood pressure and pulse rate.
■ median blood pressure (MBP) is calculated as three automatic medians of measuring that carry out in a minute, it is used to reflect the mean level of the long-term sympathetic tone of cardiovascular system, the long-term sympathetic tone of described cardiovascular system as lastingly stress measure (referring to preface part).
■ calculates the index of systolic pressure-heart rate-product (PRP) as heart running and myocardial oxygen consumption, reflects the instantaneous sympathetic tone (referring to preface part) of heart thus.
■ is (Nussbaum ﹠amp on the particular acupoint of chest; Downes 1998) measure warning system sensitivity (WSS) as the tenderness degree measurement.According to patent (Ballegaard 2004), it passes through
Measure and be used as possible the measuring of sympathetic tone.Measure WSS at left forefinger (at the back position of middle phalanx) with at acupuncture point CV 17 (referring to preface part).Write down the existence of " reflection of retreating " relevant with measured value.
The significant feature variable
WSS with respect to HbA1c.
Auxiliary actuation variable
■ is with respect to the WSS of MBP
■ is with respect to the WSS of PRP
The experimenter be required the test before last two hours in must not take food, tea, coffee, smoking, ethanol.
Everyone of WSS level＞40 wherein reduces the placebo of short-term acupuncture and rest the contrast of WSS aspect by invite participation randomized test as described below (" investigational studies 2 ").
The experimenter can withdraw from any time.
Ignorant situation (Bilnding)
To experimenter concealment hypothesis:, and make it not know these information by the level determination WSS level of glycosylated hemoglobin about research.The correlational study personnel are ignorant, but the research worker of implementing the WSS measurement must be known the inside story.Therefore, two groups of research worker cooperations, each group all is ignorant to the result of another group.Measure WSS for one group, another group is measured HbA1c, blood pressure and pulse rate.The automaton that use is used to measure blood pressure, pulse rate and HbA1c helps to make the research worker of implementing these measurements ignorant.In addition, the experimenter is apprised of and can not carries out language communication with the observer, during SO measures except stop so that when reaching the pressure sores threshold value, telling.
Sample size calculates
From previous research (breast carcinoma; Opera), can expect 1 unit of the every rising of HbA1C, WSS 10 units that can raise.Also observe, male subject has significantly lower WSS value.Based on the experience that derives from these researchs, suppose that the varying level of male/female can be explained 43% of total difference, and the combination of sex and HbA1c can be explained 45% of total difference.The impregnable hypothesis of F check checking HbA1c with α=0.05 (I type), can realize following effectiveness (powers):
N＝ 200 250 300 350 400
β=(II type) 77% 85% 91% 95% 97%
Therefore, 300 people's of plan sample size produces 91% acceptable effectiveness;
Statistical method
Main analysis uses WSS that the linear regression of HbA1c is carried out, control sex and age.Use comprises HbA1c in model III type F checks and verifies original hypothesis.
Subsequently, comprise the exploratory analysis of WSS based on above-mentioned model to any linear regression of PRP and MBP.
The design of investigational studies 2
This of the following stated research purpose is to confirm following hypothesis:
Main purpose: compare with rest with the placebo pill, acupuncture reduces warning system sensitivity
Second purpose is the discovery that confirms above-mentioned guiding research, that is:
A. when accepting standardized acupuncture and moxibustion treatment, the people with high HbA1c level has the nervous system motility of reduction, shows as the habituation aspect pressure-speed-product (PRP), MBP, saliva hydrocortisone and warning system sensitivity.
B. when accepting standardized acupuncture and moxibustion treatment, the people with low lasting stress level (measuring low serum HbA1c level) has nervous system flexibly, shows as in significant aspect PRP and the WSS and and the reaction of depositing.
Comprise comparative study between prospective, single blind, the group of three treatment groups.This research comprises 100 successive people, and they satisfy the typing standard, is assigned to one of three treatment groups at random: acupuncture, placebo and rest.
The typing standard: the age is the 18-75 masculinity and femininity in year, WSS＞40.
Exclusion standard: the women of diabetes (insulin-dependent and non-insulin-dependent), psychiatric disorders, anemia of pregnant woman and suckling, nearest 6 months with cross the general steroid medicine, in the past measured WSS, live through acupuncture and moxibustion treatment in nearest six months.
The experimenter's of participation research selection is based on following:
1) Yan Jiu hypothesis is to produce by the exploratory study based on the successive adult patient of acupuncture clinic.
2) people who comprises has represented general crowd, has the warning system sensitivity of rising, does not use apparatus and method of the present invention to carry out measurement in the past, and does not use acupuncture regularly.
In randomized clinical trial, use following method:
1) provides verbal and written data for the patient before by phone and mail/electronic mail access.
2) signature Informed Consent Form
3) raw data
4) randomization is assigned to one of three possible treatment groups (acupuncture, placebo pill or rest).
5) patient carries out 3 minutes experience time with back floating position
6) measure before the treatment: saliva hydrocortisone, pulse rate, blood pressure, by method measurement warning system sensitivity of the present invention.
7) under not changing the situation of position, the patient carries out treatment in 3 minutes: acupuncture and moxibustion treatment, placebo or rest.
8) treatment back is measured: saliva hydrocortisone, pulse rate, blood pressure, by method measurement warning system sensitivity of the present invention.
Placebo is the vitamin tablet, and it dissolves after sublingual administration.For acupuncture and moxibustion treatment, use some Zuzanli (St 36) at bilateral.With pin (disposable stainless pin,
) be inserted in the underlying muscle perpendicular to skin, the degree of depth is about 5mm, does not apply other mechanical stimulus or electricity irritation, original position kept 3 minutes.Rest in the research is defined as and keeps back floating position and experimenter or experimenter do not carry out other action.
For randomized test, all measurements and treatment are all carried out at inventor's acupuncture center.
The individual actuation variable of following measurement:
Application form
The ■ demographic statistics; Age, sex, BMI, waistline, concomitant disease and the medicine of depositing, to the self-perception of stress level, to the expected value of the effect of three kinds of TAs.
The health status that ■ is general
■ lastingly stress the existence of clinical sign
The existence of ■ occupational stress (national occupational health association, National Institute ofOccupational Health) To AMH.International list of references about the application form effectiveness
Physiologic measurement
■ measures glycosylated hemoglobin (HbA1c) from capillary blood; That is, get blood from experimenter's finger tip.With its as lastingly stress measure.
■ is by automatic monitoring record blood pressure and pulse frequency.
■ median blood pressure (MBP) is calculated as 2/3x diastolic pressure+1/3x systolic pressure.Three automatic medians of measuring that use was carried out in one minute.MHP be used to reflect cardiovascular system long-term sympathetic tone mean level and as lastingly stress measure (referring to preface part).
■ collects the saliva hydrocortisone by on-the-spot saliva sample, and the analysis of saliva is carried out at special laboratory.With its as instantaneous stress measure.
■ calculates the index of systolic pressure-heart rate-product (PRP) as heart running and myocardial oxygen consumption, reflects the instantaneous sympathetic tone of heart thus.
■ measures the warning system sensitivity (WSS) that obtains as the tenderness degree measurement as described herein on the particular acupoint of chest.It is measure by method of the present invention and measuring as sympathetic tone.At first at left forefinger (at the back position of middle phalanx) with subsequently at acupuncture point CV 17 measurement WSS.
The significant feature variable
WSS group difference with respect to three treatment groups (acupuncture, rest and placebo pill)
Auxiliary actuation variable
■ with respect to three treatment groups at the group difference aspect PRP, MBP and the saliva hydrocortisone
■ is with respect to level before the treatment of glycosylated hemoglobin (HbA1c), the dependency between the variation of the variation of WSS and PRP, MBP, saliva hydrocortisone.
Obtain the expected value relevant at baseline with the effect of three kinds of TAs.
Owing to can not realize real unwitting acupuncture test (being), use a kind of particular design, altogether with psychology variable, physiological variable and clinical effect set of variables because the special properties of described treatment.
Before begin treatment, measure the patient expected value relevant with each treatment.Use the serum HbA1c of placebo, unknown level and use objective physiological variable to make the patient ignorant.Owing to conspicuous reason, the treatment research worker must be known the inside story.Yet the influence of having deleted the expected value of treatment research worker from the hypothesis of research: effect-these information by physiology state estimating treatment before experimenter's the treatment are that the experimenter is not getable.Implement all measurements by the research worker of observed result, and make its selection ignorant to treatment, because see that from observer's angle acupuncture group, placebo treatment group and rest group have identical outward appearance, that is, patient's lower limb (having acupuncture point ST 36 on described lower limb) is covered by a piece of cloth in all therapeutic processes.The research worker of observed result when randomization and when carrying out TA not in Medical Treatment Room.In addition, by using automatic machine, can get rid of observer's expected value.The experimenter is apprised of and can not carries out language communication with observer or acupuncturist, during SO measures except stop so that when reaching the pressure sores threshold value, telling.Between the research worker and acupuncturist of observed result, exchange the timing that is only limited to described program.
Patient's notice
The patient who accepts placebo is apprised of them and accepts a tablet, and described tablet is considered to have the effect identical with acupuncture.Yet, the definite effect of pill can not be disclosed, because this can induce patient's Expected Results.The purpose that the patient is apprised of research is that the record physiology changes, and described variation can occur in two kinds of therapeutic processes, and these variations and the variation that takes place in the rest process are compared.
The experimenter is required must not take food, tea, coffee and ethanol and must not smoking in before test last two hours.
Method of randomization
Method of randomization is based on computer program.Research worker and patient that randomized selection is only treated know.The statistician does not know randomized selection yet before the data base is sent to statistical analysis.
The experimenter can withdraw from any time.Adverse events in the record process of the test.Expection does not have big danger.
Time before beginning one's study, Denmark " Datatilsynet " submitted in research, and before " Datatilsynet " approval, do not begin test.
(intention-to-treat principle, ITT), main analysis is based on all randomization experimenters according to the purpose Therapeutic Principle.
Statistics is considered
Sample size calculates
Based on previous observed result, be expected at acupuncture WSS reduction afterwards 35% in 3 minutes, and the standard deviation (SD) of the relative variation of expection WSS is 25%.When total sample size is 100 experimenters (each organizes 33 experimenters), use the t check checking of α=0.05 (I type) between acupuncture group and placebo treatment group, not have the hypothesis of difference can produce following effectiveness (type):
WSS in placebo group relatively changes 20% 18% 16% 14% 12%
β=(II type) 67% 78% 86% 92% 96%
Therefore, if the WSS in the placebo test group reduces by 15%, 100 sample size of plan can produce about 90% acceptable effectiveness.
Statistical method
Main analysis is changed to the basis relatively with the WSS's of following calculating:
WSS
After the treatment-WSS
Before the treatment/ WSS
Before the treatment
The t of use α=0.05 checks and verifies the hypothesis that does not have difference between acupuncture group and placebo treatment group.
Research obtains the approval of local Ethics Committee (Ethics Committee).
Above-mentioned discovery in guiding test provide of the present invention new aspect:
At first, the method of the state of the warning system sensitivity (WSS) that is used to measure the experimenter is provided, and it comprises that the nociception that is determined on the health or in the health depends on stimulation that the threshold value of the point of sympathetic tone applies and stimulus threshold is associated with the WSS value.Therefore, known when having correct ambient conditions, described herein stress can being replenished with the measured value of WSS with the assay method of sympathetic tone.For example, be in when not having the stress-induced factor basically or wherein having determined not exist in the environment of acute stress inducement the experimenter, the measured value of WSS is optimised.Similarly, preferred ambient (or level of activation of individual) (for example should not relate to themselves factor of inducing the sympathetic tone increase, preferred experimenter should not be in and just carry out the state that violent severe is taken exercise, because sympathetic tone is raise).In this case, the nociception that the WSS reading of the inventive method can provide this people whether to have rising for the technical staff, have thus rising WSS-this indicate again and need certain clinical intervention.
Usually, herein with measure relevant all of sympathetic tone and stress (selection of stimulus type etc.) related ins and outs and be taught in the in addition necessary method of measuring WSS that is applicable to after changing.
As mentioned above, the discovery relevant with WSS also provides possible intervention, therefore, described discovery also provides the method for regulating warning system sensitivity state, described method comprises sympathetic tone and/or stress level and/or the WSS that a) measures the patient as described herein, if and measured value shows that sympathetic tone and/or stress level raise, and then make sympathetic tone subordinate point stand the stimulation that intensity is lower than stimulus threshold in a period of time.This more low intensive experience is preferably implemented by Acupressure or acupuncture therapy.
Pressure-pain-threshold value that embodiment 12-measures by odynometer
Warning and system of defense have been the basic part of living organism surviving policy in whole evolutionary process.On skin, formed special sensor so that detect the histoclastic environmental stimulus of possibility, for organism provides the hostile environment condition is made the needed information of optimal response, and may also be attended by for example terrified or retreatment of reflex response.
This nociception system is based on polymodal receptor, and described polymodal receptor is a kind of from the fish to the level vertebrate animals and people's undifferentiated neurocyte of having same nature in interior evolution chain from start to finish.Described sensor stimulates with mechanical pressure (deleterious and non-deleterious), temperature and acidity.Two different classifications have been determined: A-Δ sensor and C-sensor with high threshold with low threshold of pain, the two is all to adjusting (1) sensitivity via cationic channel subgroup TRPV 4 (the instantaneous receptor potential vanilloid receptor of TRPV=, Transient receptorpotential vanilloid).The various exogenous and endogenic material that comprises sympathetic nerve input and parasympathetic nervous input can cause adjusting, thereby produces gate multiformity (gating diversity).
Known psychology stress suppress the pain sensation (analgesia of stress-induced) of these sensors, provides the existence potentiality by suppress the general pain sensation when fighting or runing away, and perhaps only is the salivary attitude in person's character ground when proving an abortion.Also observe the rising (hyperpathia of stress-induced) of the opposite pain sensation, mainly be confined to wound or damage, perhaps the enhanced tail of conduct of animal flicks or the pawl pressure-responsive in restriction stress process, and it all provides the existence potentiality by the structure sensitive properties that strengthens warning system separately.Similarly, have been found that cause psychology stress illusion input strengthen audition, the olfactory sensation input increases startle reflex.
Raise and the existence of relevant with ill organ/area specifically several points has become the foundation stone of east acupuncture tradition (Orientalacupuncture tradition) since several centuries in the sensitivity on the skin, ischemic heart patient's clinical observation result shows, the tenderness of particular acupoint raises and may and stress raise relevantly with sympathetic tone on breastbone, and other the point on the body surface is unaffected.Stress and ischemic heart desease between association be intensive.In addition, wherein the patient use the tenderness degree as stress biology the feedback flag thing the compound scheme of various treatments make patient's survival rate be better than general crowd.
Under this background, we guess that psychology stress increase the sensitivity of breastbone acupuncture point CV 17, and described CV 17 is positioned at and nipple and intercostal space level forward.
We at first use odynometer before and after opera performance 48 members of imperial opera chorus to be measured threshold of pain (PT).By 5 seconds interval measurements, find significant correlation (r=0.92 between first and second measured values; P＜0.0001).Compare before with performance, PT significantly reduces (33.6 pairs 38.9 of meansigma methodss) (p＜0.05) after performance.
Then, for the amplitude of the psychology stress level that increases record, the solo singer is carried out following measurement (preferably before first performance in (opening-night) performance process): 1) before performance begins; 2) just after their performance highest point and 3) when finish night.Actuation variable comprises pressure-speed-product (PRP), heart rate (HR), median blood pressure (MBP) and saliva hydrocortisone.Figure 24 shows that for all actuation variables, it all is significant changing.PT be changed significantly with PRP (r=0.54, p＜0.0001) (referring to Figure 25 a), the variation of HR (r=0.55, p＜0.0001), MBP (r=0.42, p＜0.005) and saliva hydrocortisone (r=0.28, p＜0.05) is relevant.
Dependency between PRP and the PT variation has two measured values to depart from general modfel, and shown in the arrow among Figure 25: the increase of PRP is relevant with the reduction of PT.To the demonstration of probing into of possible explanation, compare with remaining singer, these two singers have carried out high-caliber body movement (running stage and cat ladder) in the last a few minutes before measuring for the second time.
Subsequently, make 26 opera students experience the bicycle exercise test, simulation opera singer exercise mode before the lights.Figure 25 b has shown at the negative correlation (r=-0.70 of bicycle exercise period between the variation of PRP and PT; P＜0.0001).In addition, the student is measured and the mutual relation of singing audition, find the relevant (r=0.32 that is changed significantly of PRP and PT; P＜0.01).
These study prompting, experience psychology stress situation the time healthy people, and the sensitivity that relates to breastbone acupuncture point CV 17 raises, and when described situation was removed, sensitivity was recovered.Initial observed result in the opera chorist is confirmed improving under the experiment condition, at first is opera solo singer, is to obtain proof in the opera student subsequently.The variation of sensitivity and known physiology and biochemistry are stress variable relevant.In addition, one that comprises sports studies show that, although the cardiovascular system physiological change of amine is similar to the cardiovascular system physiological change of sports during the opera performance, but they relate to different phenomenons: psychology stress and sports, and opera performance comprises its two combination.
Known exercise reduces pain sensitivity and reduces psychology stress.Under this background, the variation of inferring the pain sensitivity at breastbone acupuncture point reflected psychology stress varying level.
Psychology stress measurement result an aspect be can write down stress transient change.Second aspect is to measure baseline values.Therefore, 181 continuous patients of outpatient service internal medicine acupuncture clinic are write down the rest value of the threshold of pain of acupuncture point CV17 and forefinger and HR, PRP and MPT.The rest PT of CV 17 and baseline PRP (r=0.23; P＜0.01) and HR (r=0.25; P＜0.01) significant correlation.In 63 women of the PT with rising, have the significant correlation with MBP, that is, and PT＞45 (r=0.30; P＞0.05).Compare with male's (meansigma methods is 32), the women has significantly higher PT (meansigma methods is 46) (p＜0.0001).Compare with 39 on the CV17 of acupuncture point, the median PT on the forefinger is 0 (p＜0.0001), and therefore, the PT measurement result on the forefinger does not show useful sensitivity.
Find that HR, PPR and MBP are the useful variable in stress correlation circumstance and the prognosis indicant of cardiovascular disease.In addition, Jian Kang people from the teeth outwards, it is relevant with small inflammatory reaction that resting heart rate is considered to.Having proposed common ordinary circumstance is the sympathetic nerve activation.Therefore, the significant correlation between breastbone sensitivity and cardiovascular variable has been supported the hypothesis of described research.
Figure 26 is illustrated in the PT between the patient who is divided into three groups and injures the relation of retreating between the frequency that reflects NWR, increases with 100% of pain sensitivity each group is distinguished.In patient with hyposensitivity (PT＜30), in 17% patient, observing the reflection of retreating, and being 56% at medium group, in patient, be 93% (p value＜0.0001 of group difference with hypersensitivity (PT＞60); Correlation coefficient between the existence of PT and NWR is r=1.0).
The reflection of retreating has been that the means of seeking survival-conduct in the whole evolutionary process is to the defensive reaction of potential noxious stimulation and represented the reaction of the simplest maincenter tissue to the misery stimulation.This reaction helps animal away from destructive stimulus.All probably neural modulation system all are to make up on the basis of this primary retreatment reflection.All have various NWR in the animal and human, every kind of NWR is considered to multisynaptic functional module, and this depends on the specific region of stimulation.In Malaysia and China, observed the dose dependent mutual relation between stimulating dose and the NWR size, and observer's consonance height.The differentiation of reflecting of retreating improves the existence potentiality: the stimulation of causing injury adds the defencive function of strong reflection by the reflection that strengthens (sensitization) protection injury site, and can increase the weight of to damage to the inhibition of those reflections.
Therefore, the hypothesis of described research (that is, warning system can increase the sensitivity of key position so that increase survival) obtains the support of this discovery.The existence potentiality are improved by the enhancing of the simplest non-cognitive-ability output movement reaction (reflection of retreating).In more complicated level of response, can improve the existence potentiality to individuality, described individuality has successfully stoped and the long-term relevant optimum behavioral pattern that is lower than that raises of stress hormone level with cognitive the processing by the information that obtains being carried out multiple introspection.
Figure 27 represents the result of reliability test: the 27a) measurement of 82 healthy people being carried out by HCP, and described 82 healthy people measure (r=0.94, p＜0.0001) for the first time; 27b) measurement (the r=0.97 that 181 continuous patients of internal medicine outpatient clinic is carried out by HCP; P＜0.0001); And 27c) introspection that is undertaken by 33NON-HCP, carry out (r=0.95 every day twice in two time-of-weeks; P＜0.0001).
The level of observed PT measuring reliability with carry out simultaneously non-chemically, the level of non-invasive diagnostic method is complementary, the result is multiple audiometry (r=0.70), axillary fossa to rectal temperature (r=0.73) and rectum to central temperature (r=0.94).
Pain is the active process that part is generated by multiple variation in the central nervous system in periphery and part, and described multiple variation has determined the gained of system jointly, and general purpose is to produce best existence potentiality (Woolf CJ; Salter MW 2000).Consistent therewith is that the pain sensation is subjected to understanding processing and emotion processing, attention and society factors in the brain.
Physiology's pain is caused by the special sensory receptor fiber (polymodal receptor) of innervation peripheral tissues.Neuron in the sensation input activation spinal cord, it projects cerebral cortex by the relay station in the thalamus.Deleterious input also activates the reflection of retreating, and emotion, autonomous and neurohumoral reaction.
The adjusting of sensitivity is the excitatoty reversible change of main neuron and axoneuron, and it is to be regulated by intracellular signal transduction cascade by the change of sensor/ion channel.The increase of pain sensitivity can cause the no longer normally algesiogenic situation of its moderate stimulation, (touches pain) like this or the common bigger pain (hyperpathia) of destructive stimulus generation ratio.This sensitization can carry out in periphery as in the situation of inflammation, perhaps carries out at maincenter as during the C-fiber stimulates.Spinal cord is suppressed the sensitization that machine-processed compacting can help maincenter to regulate.This compacting is responsible in the activation of the neurotransmitter γ-An Jidingsuan (GABA) by A-Δ centripetal fiber.Have the neuronic selectivity activation of the RAIC of γ-An Jidingsuan (B)-sensor and produce hyperpathia by projecting tonsil (Amygdala), described tonsil relate to fear and thus with psychology stress be relevant the zone.
Instantaneous receptor potential (TRP) passage has been represented a cationic channel family, and it all has expression in comprising nearly all cellular type of invertebrates and vertebrates.They almost all have expression in every kind of tissue and cellular type.On the polymodal receptor cell, a subfamily of TRP passage (TRPV 1-6 family) and temperature, pain are relevant with tart perception.Subgroup TRPV 4 is relevant with pressure especially, and sensation is transmitted by A and C fiber, and has significant adjusting multiformity, reflection sympathetic nerve and parasympathetic nervous input.
Under this background, can infer that viewed adjusting has the basis of functional, structural and molecules, A-Δ polymodal receptor is an amboceptor, TRVP 4 cationic channels are molecule positions of regulating.
Research series in this embodiment shows, the PT measurement on the breastbone acupuncture point CV 17 represented be used to measure transient change and baseline psychology stress new method.At present, still do not relate to stress the international substantially unanimity of measurement.Because described method is reliably and for professional and layman all to be wieldy, so discovery of the present invention demonstrates practical application widely.
Psychology stress be the intensive paathogenic factor in the metabolic syndrome, influences about 4,000 ten thousand Americans and is the risk factor of cardiovascular disease and premature death.Except these tangible application the in risk of cardiovascular diseases and prognosis management, healthy individual in the population can be benefited from described method in the following areas: write down their working environment and the psychology essence of their general life and life style, be provided at the suitable understanding reflection and the potentiality of action aspect.At animal farm, following research can concentrate on described method also be used to assist in ensuring that non-stress the probability of living environment, the nutritional quality of Related product is had remarkable influence.
The specific method step:
Use has the odynometer of following characteristics:
1) the odynometer reading is hidden, and finishes up to measurement, so that make experimenter and research worker ignorant.For analysis, use the meansigma methods of two continuous measurements.
2) the odynometer pressure that applies is converted into the logarithmic scale of the sensitivity levels similar to Dec í bel scale on the mathematics.The measured value of odynometer (PT)=Log 200-Log 100 (100* is with the threshold value of kilogram/14 kilogram expression)).The increase of 30PT unit increases (=lower threshold of pain) corresponding to 100% of sensitivity.
3) in order to prevent, when reaching 14 kilograms, pressure activates alarm sound to the infringement on the skin.
4) be combined with special-purpose rubber and measure pedal, skin is not applied deleterious stimulation so that allow to measure the pressure threshold of pain on the bone, this stimulation can produce the mensuration that replaces the skin pressure threshold value.
The carrying out that threshold of pain is measured: all measurements all are to carry out under the experimenter takes the situation of back floating position.The experimenter is apprised of and says " stopping " immediately when feeling discomfort or pain.If research worker is observed terrified or the reflection of retreating, then stop to measure.Twice measurement from carrying out at forefinger during each is measured carried out twice measurement at chest subsequently.In opera student's research (referring to following), first measured value on the same day comprises twice measurement.For remaining measured value, only use one-shot measurement, so that prevent infringement to sensory receptor.
The measuring position: 1) the acupuncture point CV 17 on the breastbone centre, discern by the pain spot of observer's palpation in the diameter with nipple and intercostal space level forward of traditional Chinese medical science acupuncture point figure (Chinese description of the point) is 5 centimetres circle.2) control point: at the dorsal part of left side forefinger upper and middle section phalanges.
By Thuasne automatic blood pressure monitor W0840 002 001 types (Microlife ref.BP-3AA1-2, BP 243-92307 Levallois-Perret Cedex, France) recording blood pressure and heart rate.For analysis, use the meansigma methods of two continuous measurements.Pressure-speed-product (PRP) is calculated as systolic pressure x heart rate (HR).Median blood pressure (MBP) is calculated as 2/3 diastolic pressure x1/3 systolic pressure.The scene obtains saliva hydrocortisone sample and passes through the radioimmunoassay methods analyst.
Expection blood pressure, heart rate, pressure-speed-sum of products saliva hydrocortisone can when the psychology stress level changes, change to some extent (R.E.Noble, Metabolism 51 (5), 37-39 (2002); B.Harl, B.Wesisshuhn, H.H.Kerscbaum.NeuroEndocrinolog Letter 27 (5), 669-674 (2006).
Imperious muscle contraction of the musculus flexor of the imperious muscle contraction in eyes, the buccal (=startle reflex) zone or cervical region and upper limb is recorded as injury in the measuring process reflection (NWR) of retreating.NWR is considered to be used to study the reliable and objective instrument (Pain 96 for V.Skljarevski, N.M.Ramadan, 3-8 (2002)) of people's pain control system.
Experimenter and research design
Expection opera singer be subjected to usually with perform relevant psychology stress (D.T.Kenny, P.Davis, J.Oates, J Anxiety Disord.18 (6), 757-777 (2004)), and expection opera solo singer is subjected to extra high stress level when their concertize peak, particularly when premiere is performed.
Research 1: for predictable under stress change condition stress for threshold of pain (PT)
Variation with physiological variable
Stage A: 48 members to imperial opera chorus before and after the performance of 3 hours operas measure.Be reliably and before performance, record owing to find the PT measured value than lower after the performance, thus initial hypothesis confirmed, and establishment stage B.
Stage B: change experimental program and stress change and reduce from the influence of obscuring factor: include only solo singer (N=26 so that improve the psychology of record; 16 women and 10 male) and preferably during the premiere performance, measure.Their mean age is 46 years old.Carrying out three measurements on the same day: 1) before the performance beginning; 2) expection they stress the performance climax of top level after immediately with 3) when finish night (, peak performance after the time in evening) as far as possible, so that the recovery of permission maximum in the limitation of research.The first and the 3rd measurement is what to carry out in singer's dressing cubicle zone, and second measurement is to carry out at interim backstage measuring station, so that make the time period between optimal representation and the measurement reduce to the shortest.Actuation variable comprises PRP, HR, MBP and saliva hydrocortisone.
Stage C: when PRP that writes down opera solo singer and PT variation, have two measured values to depart from general modfel (shown in the arrow among Figure 25 a): the increase of PRP is relevant with the reduction of PT.To the demonstration of probing into of possible explanation, compare with remaining singer, these two singers have carried out high-caliber body movement (running stage and cat ladder) in the last a few minutes before measuring for the second time.Therefore, at the not same date that separates establishment stage C in 26 opera students of two different tests of participation (singing audition and bicycle exercise test).Each test is with the rest beginning in 10 minutes and the end of back floating position.In addition, the experimenter is required not take any medicine, coffee, ethanol or Nicotiana tabacum L. in 2 hours before test, and it is moving to be required that last hour before test is not engaged in ass work.Their mean age is 27 years old, 11 male and 15 women.
Singing test is made up of twice measurement: 1) as close as possiblely sing audition, but have a rest after 10 minutes and 2) just after audition, but also be after 10 minutes have a rest.Therefore, any variation of the PRP of record and PT is all relevant with the recovery after the audition.
Bicycle test has the Kettler Ergometer bicycle Xc type (X3) of Siemens elektronik cadiofitnes/ SD 4,8,5,9 (Freizeit MarkeKettler, Heins Kettler GmbH ﹠amp; Co, KG post fach 1020, D-59463Ense-Parsit carries out on Germany).And comprise 4 measurements: 1) after having a rest 10 minutes, 2) after 2 minutes take exercise, purpose is that the PPR when making PRP with rest compares rising 25%, 3) after another 2 minutes take exercise, purpose be the PPR when making PRP with rest compare raise minimum 40%, but be lower than age-based estimation maximum working load/heart rate maximum working load 80%.Measure for the 4th time is after having a rest 10 minutes.
Depend on that independent student is fit to the estimation of situation to its muscle power, women's workload is 50/75 watt and 80 rev/mins (rpm), and the male is 75/100 watt and 80rpm.For second exercise period, it is that 75/100/125 watt and 90/100/110rpm and male are 100/150/200 watt and 90/100/110rpm that workload is increased to the women, and also bicycle may be applied and be increased to 3 minutes.Have an experimenter to be excluded, because his PRP is elevated to 33.300 from 9700 during second exercise test, heart rate is 197 (limit heart rate of adjusting by 80% age is 154).
181 the successive patients (126 women and 55 male) that comprise private internal medicine outpatient clinic.Their mean age is 58 years old.Their diagnosis is: cancer 55, heart disease 49, stress 19 and other 58.Under back floating position rest 10 minutes and ignorant situation, carry out the existence whether measurement of PT rest value, blood pressure, heart rate and NWR by two independent seminar.Measure PT and NWR by a group, another group is measured blood pressure and heart rate.For determining of PT, the measurement on the acupuncture point of breastbone CV 17 is considered to active measurement point, and the measurement on the forefinger is the measuring position in contrast.For clinical practice, the PT ratio has been made 3 grades of scales, increase PT＜30 corresponding to per 100% of sensitivity; 30＜=PT＜60, PT=＞60.Use it for the comparison of PT measurement and NWR.
The test of research 4.PT measuring reliability
Carry out the test of PT measuring reliability in three kinds of situations, carry out twice PT in each case and measure, 5 seconds time is arranged between the measurement: by the measurement that HCP carries out 103 healthy people, described 103 healthy people measure for the first time; 2) measurement of 181 continuous patients of internal medicine outpatient clinic being carried out by HCP; And c) introspection that is undertaken by 33NON-HCP, carry out twice every day in two time-of-weeks.
Statistics
Add up by SAS software by statistician independently.5% as significance limit.
Ethics
All experimenters obtain verbal and written information, and sign written book in the know before measuring for the first time.Local Ethics Committee has ratified the research carried out in opera singer and student.Remaining research is to implement as the part of daily curative activity in the clinic, and described curative activity meets Denmark's medical control (Danish medicalregulations) and ICH guide about Good Clinical Practice (good clinicalpractice) (7).
Embodiment 13
This embodiment has proved 1) instantaneous stress during the generation of optimal representation, 2) measured value that uses motility as instantaneous stress and lastingly stress between difference and 3) introspection in 12 weeks, the cognition of gained information is handled and carry out the effect that suitable action produces.With reference to figure 28-30.
Physiology's background:
Instantaneous stress situation in the precondition of optimal representation be the activation of organism stress.This shows as the increase of WSS and DRS
In order to carry out stress, need the brain extra work, thereby to oxygen need increase.For the muscle of the physics aspect of implementing defense reaction also is same.Therefore, heart need be worked more.This shows as heart working increases, be measured as PRP (product of heart rate x systolic pressure) (PRP), the increase of heart rate (HR), median blood pressure (MBP).
Above-mentioned heart-physiological variable not only be subjected to stress influence, and be subjected to the influence of physical exertion, described physical exertion is the light to moderate exercise on bicycle for example.Therefore, these measured values can not be as independently stress measured value, but with WSS and DRS combination the time, provide about stress useful measuring.
Motility represents that organism suitably adjusts the ability of function in response to environmental change.Good motility means that organism responds this variation fast and fully and makes adjustment.For instantaneous stress concrete condition, this is meant that stress is fully activated at the peak place of performance and rebuilding body inner equilibrium apace when this situation finishes.
In this embodiment, use three kinds of independent test situation:
A) when singing audition, test: measure with the following time period: 1) having a rest after 10 minutes and before the audition, 2) just after audition and 3) after the rests in 10 minutes after measuring for the second time.
B) test 1 by bicycle test) after having a rest 10 minutes, 2) corresponding to heart working is increased to equal 4 minutes of singing audition take exercise after and 3) having a rest 10 minutes after.
C) using computing and time and performance strain to be combined in 10 minutes-spirit tests in stress checking: 1) after having a rest 10 minutes, and 2) in process of the test, carry out twice and 3) after rest 10 minutes.
The result is reported among Figure 28-30 of accompanying drawing.
Claims (123)
1. measure the method for the state of experimenter's sympathetic tone and/or stress level and/or warning system sensitivity (WSS)/defense reaction/reflex sensitivity (DRS), may further comprise the steps: measure stimulation that applies with stimulus threshold and the stimulation that applies in same threshold at one or more sympathetic tone subordinate point measurements in one or more sympathetic tone neutral points, perhaps measure the stimulation that applies with threshold value at one or more sympathetic tone subordinate points and randomly with described threshold value with measure in advance or predetermined calibration threshold value compares.
2. the process of claim 1 wherein that the threshold value that stimulates is the nociception threshold value that stimulates.
3. claim 1 or 2 method, wherein the stimulation that is applied is to provide by the mechanical stimulus that applies.
4. the method for claim 3, wherein the mechanical stimulus that is applied provides by applied pressure.
5. the method for claim 3, wherein the mechanical stimulus that is applied is to provide by the vibration force that applies.
6. claim 1 or 2 method, wherein the stimulation that is applied is to provide by the thermostimulation that applies.
7. the method for claim 6, wherein the thermostimulation that is applied is to provide by thermal source that applies or low-temperature receiver.
8. claim 1 or 2 method, wherein the stimulation that is applied is to provide by the electricity irritation that applies.
9. the method for claim 8, the electricity irritation that wherein applies provides by alternating current or unidirectional current.
10. claim 1 or 2 method, wherein the stimulation that is applied is to provide by the radiation that applies.
11. the method for claim 10, the radiation that wherein applies are to provide by the infrared light that applies, visible light and/or ultraviolet light or its combination spectrum.
12. the method for claim 1 or 2, wherein the stimulation that is applied is to provide by the chemical stimulation that applies.
13. the method for claim 12, wherein the chemical stimulation that is applied is to provide by organic compound that applies or inorganic compound.
14. the method for claim 1, wherein the stimulation that is applied at sympathetic tone subordinate point is the direct stimulation of at least a polymorphism receptor cell, and the threshold value of wherein one or more sympathetic tone subordinate points is excitation thresholds of described at least a polymorphism receptor cell.
15. the method for claim 14, wherein said direct stimulation are selected from AC stimulates, DC stimulates, uses neurotransmitter to carry out stimulation and chemical stimulation.
16. each method in the aforementioned claim wherein measure to be to carry out by the system that is used to measure the stimulation that is applied.
17. each method in the aforementioned claim is to carry out on the clavicle upside in front and/or carrying out and/or carry out on finger and/or toe on corresponding to the spinal column of TH 10-11 in the back with the measurement of the stimulation that stimulus threshold was applied in one or more sympathetic tone neutral points wherein.
18. each method in the aforementioned claim, carry out at one or more sympathetic tone subordinate points one or more positions of wherein measuring the stimulation that is applied with stimulus threshold and be on skin or in the skin, and the innervation ground, one or more position on the described skin or in the skin distributes corresponding to the nerve of the heart of sympathetic nervous system.
19. each method in the aforementioned claim, wherein measure with the stimulation that applies with stimulus threshold of one or more sympathetic tone subordinate points and carry out: on the St 18 and/or Per 1 and/or spinal column between nipple and the anterior axillary fold between two ribs under intermediary C.V.17 of breastbone and/or the nipple, wherein select the pain spot of described point corresponding to TH 3-6 at following one or more points.
20. quantitatively and/or qualitative determination comprise people's the sympathetic tone of animal and/or the method for stress level and/or WSS/DRS state, described method comprises:
A) stored calibration threshold value and stimulus threshold, described calibration threshold value is the quantitative measure of the nociception threshold value of sympathetic tone neutral point on the described animal health or in the health, and described stimulus threshold is the quantitative measure of the nociception threshold value of sympathetic tone subordinate point on the described animal health or in the health;
B) by stimulus threshold and calibration threshold value being compared the readout that calculates WSS and/or DRS and/or sympathetic tone and/or stress level, thereby the readout of WSS and/or DRS and/or sympathetic tone and/or stress level is measuring of human warning system sensitivity and/or sympathetic tone and/or stress level.
21. quantitatively and/or qualitative determination comprise people's the WSS/DRS state of animal and/or the method for sympathetic tone and/or stress level, described method comprises:
A) stored calibration threshold value and stimulus threshold, described calibration threshold value is the quantitative measure of polymorphism receptor cell excitation threshold in the sympathetic tone neutral point in the animal health or on the health, and described stimulus threshold is the quantitative measure of the polymorphism receptor cell excitation threshold in the sympathetic tone subordinate point in the animal health or on the health; Subsequently
B) by stimulus threshold and calibration threshold value relatively being calculated the readout of warning system sensitivity, thereby the readout of warning system sensitivity and/or sympathetic tone and/or stress level is warning system sensitivity of animal and/or measuring of sympathetic tone and/or warning system sensitivity.
22. the method for claim 20 or 21, wherein calibration threshold value is that measure in advance or the predetermined steady state value of permanent storage.
23. the method for claim 20 or 21, wherein calibration threshold value is zero, thereby readout equals the stimulus threshold or the function of stimulus threshold.
24. the method for claim 20, wherein calibration threshold value and stimulus threshold are simultaneously-measured basically.
25. the method for claim 24, wherein the readout of sympathetic tone is the mathematical combination of calibration threshold value and stimulus threshold.
26. the method for claim 24, wherein said readout are the functions of the ratio between calibration threshold value and the stimulus threshold, for example are monotonic functions.
27. the method for claim 24, wherein said readout are the functions of the difference between calibration threshold value and the stimulus threshold.
28. be used to control the method for process of patient's therapeutic scheme, the effectiveness of wherein said scheme and/or patient's compliance depend on described patient's sympathetic tone and/or stress level and/or WSS and/or DRS level, described method comprises
I) during therapeutic scheme one or many measure described patient's sympathetic tone and/or stress level and
Ii) the composite measurement result of the measured value of the interests that obtain from therapeutic scheme based on the patient and the sympathetic tone the step I and/or stress level and/or WSS and/or DRS level adjusts therapeutic scheme.
29. the method for claim 28, wherein the mensuration in the step I is carried out according to each method among the claim 1-27.
30. the method for claim 28 or 29, wherein said therapeutic scheme is selected from: use the treatment of SSRI (selective serotonin reuptake inhibitor); Treated by the psychopharmacology of the imbalance of psychology, spirit or the behavior that stress influence, comprise depression, other emotionally disturbed, addiction, dependent conditions, neurosis and suicide; Progress on Insulin Treatment in Diabetes; Nicotine replacement therapy as the auxiliary treatment of giving up smoking; The hormone therapy of post-menopause syndrome; Hormone or other Therapeutic Method about reproduction, fertility and miscarriage treatment; The anti-inflammatory agent treatment of acute and chronic inflammation; The anti-infective therapy of infectious disease; The treatment of the hypothyroidism or the hyperthyroidism patient's condition; Treatment about Dental Hygienist; The treatment of using cardiovascular drugs to carry out to heart, blood vessel and kidney disease; Use gastrointestinal drug to ulcer, irritable bowel syndrome, malabsorption, feel sick and treatment that other symptom is carried out; The pharmacological treatment that the medicine of use reduction body weight carries out; Exercise plan; Loosen plan; Diet program; Consulting or guidance; Stress governing plan; Individual Development Plan; The performance plan; With self-nursing care plan.
31. be used to prevent or alleviate undesirable or do not have the method that stress or reduce patient's WSS/DRS of effect that described method comprises
A) according to each method among the claim 1-27 measure patient's sympathetic tone and/or stress level and/or WSS and/or DRS level and
B) if the measured value among the step a shows the sympathetic tone of rising and/or the WSS and/or the DRS level of stress level and/or rising, sympathetic tone subordinate point is stood than the more low intensive stimulation of stimulus threshold in a period of time.
32. the method for claim 31, it comprises after step b in addition
C) measure patient's sympathetic tone and/or stress level and/or WSS and/or DRS level according to each method among the claim 1-27, if and measured value does not show that the rising degree of sympathetic tone and/or stress level and/or WSS and/or DRS level reduces, then make sympathetic tone subordinate point in a period of time different, stand with the time period in the step a) than the lower stimulation of stimulus threshold intensity and
D) repeating step c shows up to measured value that the rising degree of sympathetic tone and/or stress level and/or WSS and/or DRS level is compared with the measured value among the step a and decreases.
33. the method for claim 31 or 32 wherein makes sympathetic tone subordinate point stand low stimulus intensity and comes the indicating correct stimulus intensity to control by visible or audible indication.
34. be used for the method for the prognosis or the prevention of disease of patient, comprise 1) measure patient's WSS and/or DRS state and/or sympathetic tone and/or stress level, subsequently 2) provide the prognosis of disease for the patient by the measurement result in the integrating step 1 in prognosis is measured, compare with the prognosis that shows higher sympathetic tone and/or stress level and/or WSS and/or DRS level in the measurement result of step 1, sympathetic tone that the measurement result demonstration in the step 1 is low and/or stress level and/or WSS and/or DRS level are better prognosis.
35. the method for claim 34, wherein the mensuration in the step 1 is carried out according to each method among the claim 1-27.
36. the method for claim 34 or 35, wherein said disease is selected from following group:
Acute, the subacute or chronic struvite patient's condition;
Wherein immunoreation state that human organs is damaged or wherein inadequate function of immune system cause the state of the impaired and/or disease of function;
Acute, subacute or chronic infectious disease;
Be subjected to the cardiovascular disorder of sympathetic tone influence, for example cyclical shock, atherosclerosis, thrombosis, the ischemic patient's condition, infraction, arrhythmia, hypertension;
The vegetative growth disorder;
Acquired metabolism disorder;
Poison or because the somatic damage that machinery, heat, electricity or radiant energy cause;
Be subjected to the disorder of psychology, spirit or the behavior of sympathetic tone influence, for example the dependent conditions of depression or other emotionally disturbed, addiction or any kind, neurosis, suicide, sleep disordered, tired, have a feature and complaint stress be relevant psychological and/or spirit;
The fertility of masculinity and femininity reduces;
Be subjected to gynecological's obstacle of sympathetic tone influence, for example premenstrual tension syndrome, dysmenorrhea, climacteric problem, hyperemesis gravidarum, preeclampsia and convulsions, premature labor, situs inversus viscerum, induction of labour, postpartum hemorrhage;
Be subjected to the otolaryngology disorder of sympathetic tone influence, for example tinnitus and presbyacusis;
Be subjected to the dermatological obstacle of sympathetic tone influence, for example pruritus;
With the gastrointestinal disease of stress sensitive clinical sign and symptom, for example gastric duodenal ulcer, irritable bowel syndrome, malabsorption, diarrhoea, constipation, nauseating and vomiting;
Neurological disorder, for example tension headache, migraine, cerebral concussion, hypercortisolism, parkinson, Alzheimer, intracranial wound and neuropathy;
Endocrine regulation, for example diabetes, hypothyroidism, hyperthyroidism, adrenal cortex disorder, adrenal medulla disorder, hypothalamus disorder, hypophysis disorder and polycystic ovary syndrome;
Allergy for example is reflected at the allergy in skin, bronchus and the gastrointestinal tract;
With the lung disease of impaired gas exchange, for example bronchitis and emphysema;
The disease of joint and bone, for example acute or chronic arthritis and osteoporosis;
Form the relevant disorder of change, for example obesity, body weight loss, cachexia with body weight;
Sodium and the water storage property stayed morbid state, for example heart failure, renal failure, liver failure; With
Pain.
37. be used to measure the system of sympathetic tone and/or stress level and/or the WSS/DRS state of the animal that comprises the people, described system comprises:
A) memory device is used for being stored on the animal body or nociception calibration threshold value that the sympathetic tone neutral point of animal body is measured and be used for being stored on the animal body or the nociception stimulus threshold of the sympathetic tone subordinate point mensuration of animal body;
B) electronic circuit, it is programmed for and is used for nociception calibration threshold value and nociception stimulus threshold are carried out date processing, so that obtain measured value; With
C) be used for the animal health is applied the user's operating equipment that causes uncomfortable stimulation and is suitable for storing user's operation store equipment of operating the nociception stimulus threshold of generation owing to first user;
D) be used for the animal health is applied the user's operating equipment that causes uncomfortable stimulation and is suitable for storing user's operation store equipment of operating the nociception stimulus threshold of generation owing to second user;
Wherein saidly cause that uncomfortable stimulation comprises 1) vibration and/or 2 that applies by first vibration base) heat and/or 3 that applies by first heating base) apply by the first electricity pedestal, and wherein be used to apply the stimulation that the equipment that causes uncomfortable stimulation is suitable for applying to be increased gradually, described memory device is suitable for storing the irritation level in the moment that corresponds respectively to first and second users operation.
38. the system of claim 37, wherein calibration threshold value is that measure in advance or the predetermined steady state value of permanent storage.
39. the system of claim 37, wherein said calibration threshold value are zero.
40. the system of claim 38 or 39 wherein is used for applying the equipment that causes uncomfortable stimulation and is comprised in first module, and wherein said electronic circuit is comprised in Unit second.
41. the system of claim 40, wherein said Unit first and second are suitable for allowing to carry out radio communication between first module and Unit second.
42. the system of claim 38 or 39 wherein is used for applying the equipment and the described electronic circuit that cause uncomfortable stimulation and is integrated into same device.
43. each system among the claim 37-42, wherein said vibration base comprises globular basically or hemispheric vibration head.
44. the system of claim 43, the diameter of wherein said vibration head for example is 0.05mm-0.5mm less than 1cm, perhaps less than 0.5mm, for example is 1mm-4mm.
45. the system of claim 43 or 44, it comprises magnetic actuator in addition.
46. the system of claim 45, wherein said actuator is arranged along the axle of wire basically.
47. the system of claim 45 or 46, wherein said actuator comprises slide bar and a plurality of slide units of arranging along described slide bar.
48. the system of claim 47, wherein said slide unit defines at least one circumferential groove, is used to support to center on the coiling that slide unit twines.
49. each system among the claim 45-48, it comprises a plurality of magnets and spacer in addition.
50. the system of claim 49, wherein said slide bar defines chamber or hole inner, longitudinal extension, and wherein said magnet and spacer alternately are arranged in described sliding cavity or the hole.
51. each system among the claim 47-50, wherein slide bar is with reducing the coated materials that rubs.
52. each system among the claim 49-51 arranges that wherein described magnet is substantially perpendicular to the magnetic field of described slide bar in order to generation.
53. each system among the claim 48-52, it comprises the control unit of the electric current alternate in the feasible coiling in addition.
54. the system of claim 53 arranges that wherein described magnetic actuator is in order to produce vibration by the electric current that alternately changes in the coiling.
55. be used to measure the system of sympathetic tone and/or stress level and/or the WSS/DRS state of the animal that comprises the people, described system comprise be suitable in second vibration force of the vibration base that applies external vibration power on the health of animal, the pick off that is used to measure the vibration force that is applying on the health by vibration base, first vibration force that is suitable for storing respectively measurement and measurement with vibration head and be suitable for calculating first vibration force that expression measures and second vibration force of measurement between the electronic circuit of readout of ratio.
56. the system of claim 55, it comprises the sensing device that is used to show readout in addition.
57. the system of claim 55 or 56, wherein vibration base and pick off are integrated in the first module, and wherein said electronic circuit is integrated in Unit second.
58. the system of claim 57, wherein said Unit first and second are adapted to allow to carry out radio communication between first module and Unit second.
59. the system of claim 55, wherein vibration base, pick off and described electronic circuit are integrated in the same device.
60. each system among the claim 55-59, the vibration head of wherein said vibration base is for globular or hemispheric basically.
61. the system of claim 60, the diameter of wherein said vibration head is preferably 0.05mm to 0.5mm less than 1cm.
62. each system among the claim 55-61, wherein said pick off comprises the force transducer of pressure drag.
63. each system among the claim 55-62, described system are portable and provide power by one or more batteries.
64. each system among the claim 56-63, wherein said sensing device comprises electronic displays.
65. each system among the claim 56-64, it is (0,1,2,3) in several (for example 4) discrete readout that wherein said electronic circuit can be suitable for measuring readout, and the ratio of first measured value and second measured value is designated as the discrete readout (0,1,3,4) that shows on sensing device.
66. the system of claim 65, wherein said discrete readout (0,1,2,3) can and first measured value and second measured value between ratio disproportionate.
67. each system among the claim 55-66, wherein said electronic circuit is suitable for calculating first measured value and second measured value that calculates as the meansigma methods of a plurality of measured values as the meansigma methods of a plurality of measured values.
68. the system of claim 37-54, wherein the area of the contact surface of heating base is less than 4cm
2, for example be 1-2cm
2, perhaps less than 1cm
2, for example be 0.5-1cm
2
69. the system of claim 68, it comprises control unit in addition, and described control unit is used to change the temperature of contact surface.
70. the system of claim 69, wherein said control unit raises the temperature of contact surface, up to reaching built-in maximum temperature or moving up up to the User break temperature.
71. the system of claim 69 or 70, wherein said contact surface cools off by natural cooling.
72. be used to measure the system of sympathetic tone and/or stress level and/or the WSS/DRS state of the animal that comprises the people, described system comprises having the heating base that is suitable for applying hot contact surface on the animal health, the pick off that is used to measure the temperature that is applied by heating base on health, is suitable for storing respectively first and measures the electronic circuit that temperature and second is measured temperature and is suitable for calculating the readout of representing the ratio between the first measurement temperature and the second measurement temperature.
73. the system of claim 72, it comprises the sensing device that is used to show readout in addition.
74. the system of claim 72 or 73, wherein heating base and pick off are integrated in the first module, and wherein said electronic circuit is integrated in Unit second.
75. the system of claim 74, wherein said Unit first and second are adapted to allow to carry out radio communication between first module and Unit second.
76. the system of claim 72, wherein said heating base, pick off and described electronic circuit are integrated in the same device.
77. each system among the claim 72-76, wherein the contact surface area of heating base is less than 4cm
2, be preferably 1-2cm
2
78. each system among the claim 72-77, wherein said pick off comprises the thermosensitive type pick off.
79. each system among the claim 72-78, described system are portable and provide power by one or more batteries.
80. each system among the claim 73-79, wherein said sensing device comprises electronic displays.
81. each system among the claim 73-80, it is (0,1,2,3) in several (for example 4) discrete readout that wherein said electronic circuit is suitable for measuring readout, and the ratio of first measured value and second measured value is designated as the discrete readout (0,1,3,4) that shows on sensing device.
82. the system of claim 81, wherein said discrete readout (0,1,2,3) and the ratio between first measured value and second measured value are disproportionate.
83. each system among the claim 72-82, wherein said electronic circuit is suitable for calculating first measured value and second measured value that calculates as the meansigma methods of a plurality of measured values as the meansigma methods of a plurality of measured values.
84. each system among claim 37-54 and the 68-71, wherein said electronic pedestal comprises globular basically or hemispheric electrical header.
85. the system of claim 84, the diameter of wherein said electrical header for example is 0.05mm-0.5mm less than 1cm, perhaps less than 0.5mm, for example is 1mm-4mm.
86. the system of claim 84 or 85, it comprises electric actuator in addition.
87. the system of claim 86, its comprise in addition make electric current can be in electrical header mobile control unit.
88. the system of claim 87, wherein said control unit can make alternating current change into unidirectional current in addition, and vice versa.
89. the system of claim 87 or 88 wherein is provided with control unit and improves the unidirectional current that flows into electrical header, up to reaching the electric current that built-in maximum current or User break increase progressively.
90. the system of claim 87 or 88 wherein is provided with the frequency that control unit improves the alternating current that flows into electrical header, up to reaching the frequency that built-in highest frequency or User break increase progressively.
91. be used to measure the sympathetic tone of the animal that comprises the people and/or the system of stress level and/or WSS/DRS level, described system comprise have the electronic pedestal, the pick off that is used to measure the electric power that is applying on the health by electronic pedestal that are suitable at the electrical header that applies external power on the health of animal, be suitable for storing respectively second electric power of first electric power of measurement and measurement and be suitable for calculating first electric power that expression measures and second electric power of measurement between the electronic circuit of readout of ratio.
92. the system of claim 91, wherein said system comprises the sensing device that is used to show readout.
93. the system of claim 91 or 92, wherein electronic pedestal and pick off are integrated in the first module, and wherein said electronic circuit is integrated in Unit second.
94. the system of claim 93, wherein said Unit first and second are adapted to allow to carry out radio communication between first module and Unit second.
95. the system of claim 91, wherein electronic pedestal, pick off and described electronic circuit are integrated in the same device.
96. each system among the claim 91-95, the electrical header of wherein said electronic pedestal is for globular or hemispheric basically.
97. the system of claim 96, the diameter of wherein said electrical header is preferably 0.05mm to 0.5mm less than 1cm.
98. each system among the claim 91-97, wherein said pick off comprises electric transducer.
99. each system among the claim 91-98, described system are portable and provide power by one or more batteries.
100. each system among the claim 92-99, wherein said sensing device comprises electronic displays.
101. each system among the claim 92-100, it is (0,1,2,3) in several (for example 4) discrete readout that wherein said electronic circuit can be suitable for measuring readout, and the ratio of first measured value and second measured value is designated as the discrete readout (0,1,3,4) that shows on sensing device.
102. the system of claim 101, wherein said discrete readout (0,1,2,3) and the ratio between first measured value and second measured value are disproportionate.
103. each system among the claim 91-102, wherein said electronic circuit is suitable for calculating first measured value and second measured value that calculates as the meansigma methods of a plurality of measured values as the meansigma methods of a plurality of measured values.
104. the measured value of the nociception (hyperpathia) that raises is used for the purposes of definite experimenter's WSS/DRS state.
105. the measured value of polymorphism receptor cell excitation threshold is used for the purposes of definite experimenter's warning system sensitivity state.
106. be used for the method for definite experimenter's myocardial oxygen consumption, described method comprises according to each method among the claim 1-27 measures experimenter's sympathetic tone and/or stress level and/or warning system sensitivity state and based on determining the myocardial oxygen consumption level with the pre-determined relevancy of the measured value of sympathetic tone and/or stress level and/or warning system sensitivity state.
107. the method for claim 106, wherein said dependency is based on the dependency between predetermined sympathetic tone and/or stress level and/or WSS and/or DRS measured value and PRP (the pressure speed product) measured value.
108. be used to measure the method for experimenter's cardiac performance, described method comprises according to each method among the claim 1-27 to be measured under stress state and at rest period respectively, and based under stress state and determine experimenter's cardiac performance in the mathematical combination of the measured value of rest period.
109. the method for claim 108, that wherein said mathematical combination is selected from is poor, ratio and any monotonic function thereof.
110. be used for determining indirectly the method for the glycosylated hemoglobin level of diabetic subjects, described method comprises according to each method among the claim 1-27 to be measured, and determines the glycosylated hemoglobin level as the monotonic function of described measured value.
111. the method for claim 110 has wherein pre-determined WSS and/or DRS level that described experimenter is not subjected to high-caliber chronic stress or has rising.
112. be used for diabetic subjects according to claim 31-33 each prevent/reduce stress method, comprise measured value with at least one glycosylated hemoglobin measured value reinforcing stimulus threshold value.
113. the method for claim 112, the measured value indication experimenter who wherein indicates the glycosylated hemoglobin level to raise is in high-caliber long-term stress state and/or has the WSS and/or the DRS level of rising.
114. each method among the claim 1-27, be used to monitor the experimenter's who experiences investigation test stress level and/or character and/or WSS and/or DRS level, described investigation test is to have and character that stress be relevant or the test with the responsive character of warning system possibility.
115. be used to measure the method for experimenter's warning system sensitivity (WSS), it point that comprises that the nociception that is determined on the health or in the health depends on sympathetic tone is sentenced stimulation that threshold value applies and stimulus threshold is associated with the WSS value.
116. the method for claim 115, wherein said experimenter is in the environment that the factor of not bringing out acute stress basically maybe may make the other factors that the sympathetic tone of rising raises again.
117. the method for claim 115 or 116, wherein the measurement of the stimulation that is applied is carried out as limiting in each among the claim 1-27.
118. be used to regulate the method for warning system sensitivity state, described method comprises a) according among claim 1-27 and the 115-117 each measures patient's sympathetic tone and/or stress level and/or WSS, if and measured value shows that sympathetic tone and/or stress level and/or WSS raise, then make the low intensive stimulation that in a period of time, stands to compare of sympathetic tone subordinate point with stimulus threshold.
119. the method for claim 118, wherein said more low intensive stimulation are selected from Acupressure, acupuncture therapy and to the direct stimulation of polymorphism receptor cell.
120. be used for determining for example method that whether raises of people's stress level and/or sympathetic tone and/or WSS level of animal, described method comprises determines that animal has in response to the injury retreatment reflection (NWR) that stimulates, described stimulation is following stimulation: do not cause NWR in its most of individual animals in the colony of WSS that has normal sympathetic tone or be not subjected to stress or not having raising and/or DRS level, but cause NWR in the most of individual animals in the colony of the WSS of the sympathetic tone with rising or high stress level or rising and/or DRS level
Wherein the NWR observed result in response to described stimulation is that described animal has the sympathetic tone of rising and/or the indication of stress level and/or WSS and/or DRS level.
121. be used to reduce the experimenter's that these needs are arranged the sympathetic tone level and/or the method for stress level and/or pain perception and/or WSS and/or DRS level, described method comprises
A) stimulate experimenter's polymorphism receptor cell, so that measure excitation threshold, wherein preferred stimulation is the mode by electricity irritation;
B) monitoring comes from the pulse of importing into of polymorphism receptor cell in response to the stimulation of step a);
C) if the excitation threshold that the monitoring display in the step b) reduces, this be psychology stress and/or the indication that raises of WSS and/or DRS level, then stimulate efferent nerve fiber with the physiological status that changes the experimenter and
D) repeating step a)-c).
122. the method for claim 121, wherein the stimulation efferent nerve fiber in the step c) comprises peridural spinal cord stimulation.
123. be used for the closed circuit device of the controlled stimulation of efferent nerve fiber, it comprises
-be used for the polymorphism receptor cell is applied the equipment of electricity irritation,
-be used to measure from the polymorphism receptor cell and/or spread out of the equipment that imports pulse into of motor neurocyte;
-be used for the equipment that pulse and standard value compare that imports into that will measure;
-be used for efferent nerve fiber is applied the equipment of electricity irritation; With
-be used for according to the equipment of relatively controlling the electricity irritation that efferent nerve fiber is applied that imports pulse and standard value into.
Applications Claiming Priority (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US84298406P | 2006-09-08 | 2006-09-08 | |
| DKPA200601159 | 2006-09-08 | ||
| US60/842,984 | 2006-09-08 | ||
| DKPA200601321 | 2006-10-11 | ||
| US60/829,068 | 2006-10-11 | ||
| DKPA200700190 | 2007-02-02 | ||
| EP07109765.3 | 2007-06-06 | ||
| US60/924,986 | 2007-06-07 |
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| CN101578065A true CN101578065A (en) | 2009-11-11 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNA2007800416744A Pending CN101578065A (en) | 2006-09-08 | 2007-09-10 | Method of utilising measurements of threshold of pain |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102145205A (en) * | 2010-02-09 | 2011-08-10 | 大学共同利用机关法人自然科学研究机构 | Pain sensory nerve stimulation apparatus |
| CN102579014A (en) * | 2012-04-07 | 2012-07-18 | 西安电子科技大学 | Cold/hot pain stimulation system |
| CN103356291A (en) * | 2013-04-24 | 2013-10-23 | 华南理工大学 | Medical pain stimulation instrument |
| CN109564229A (en) * | 2016-07-11 | 2019-04-02 | 兰维尔健康有限公司 | The method of diagnosis correlation based on taste identification |
| CN112118784A (en) * | 2018-01-08 | 2020-12-22 | 华纳兄弟娱乐公司 | Social interaction application for detecting neurophysiological state |
| CN112218575A (en) * | 2018-05-01 | 2021-01-12 | 皇家飞利浦有限公司 | Device for determining stress and/or pain levels |
| CN115474902A (en) * | 2022-09-30 | 2022-12-16 | 山东大学 | A human body pressure threshold detection device and detection method |
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2007
- 2007-09-10 CN CNA2007800416744A patent/CN101578065A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102145205A (en) * | 2010-02-09 | 2011-08-10 | 大学共同利用机关法人自然科学研究机构 | Pain sensory nerve stimulation apparatus |
| US10543356B2 (en) | 2010-02-09 | 2020-01-28 | Inter-University Research Institute Corporation | Pain sensory nerve stimulation apparatus |
| CN102579014A (en) * | 2012-04-07 | 2012-07-18 | 西安电子科技大学 | Cold/hot pain stimulation system |
| CN102579014B (en) * | 2012-04-07 | 2014-03-12 | 西安电子科技大学 | Cold/hot pain stimulation system |
| CN103356291A (en) * | 2013-04-24 | 2013-10-23 | 华南理工大学 | Medical pain stimulation instrument |
| CN109564229A (en) * | 2016-07-11 | 2019-04-02 | 兰维尔健康有限公司 | The method of diagnosis correlation based on taste identification |
| CN112118784A (en) * | 2018-01-08 | 2020-12-22 | 华纳兄弟娱乐公司 | Social interaction application for detecting neurophysiological state |
| US12274551B2 (en) | 2018-01-08 | 2025-04-15 | Warner Bros. Entertainment Inc. | Content generation and control using sensor data for detection of neurological state |
| CN112218575A (en) * | 2018-05-01 | 2021-01-12 | 皇家飞利浦有限公司 | Device for determining stress and/or pain levels |
| CN115474902A (en) * | 2022-09-30 | 2022-12-16 | 山东大学 | A human body pressure threshold detection device and detection method |
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