Morphine

Chronic opioid receptor (OR) activation by morphine causes distinct cellular adaptations responsible for the development of tolerance. The present study examines the effect of chronic morphine exposure on the ability of high-efficacy agonists to mediate �-OR (DOR) and �-OR (MOR) uncoupling and internalization, two regulatory mechanisms contributing to rapid desensitization of OR function. Chronic morphine treatment (1 �M; 72 hr) of DOR carrying neuroblastoma x glioma (NG108-15) hybrid cells, a prototypical model system frequently used to study cellular aspects of opioid tolerance, completely blocked the capacity of [D-Ala 2, D-Leu 5]enkephalin (DADLE) and etorphine to desensitize opioid-stimulated [ 35 S]GTP�S binding and to mediate DOR internalization. Similar findings were obtained on stably DOR- and MOR-transfected human embryonic kidney (HEK) 293 cells. Chronic morphine treatment also heterologously

The practice of prescribing opioid drugs for opioid dependent patients in the U.S. has been subjected to special government scrutiny for almost 100 years. From 1920 until 1964, doctors who used opioids to treat addicts risked federal and/or state criminal prosecution. Although that period ended when oral methadone maintenance was established as legitimate medical practice, public concern about methadone diversion

Effect of mitragynine, an indole alkaloid isolated from Thai medicinal plant kratom (Mitragyna speciosa), on electrically stimulated contraction was studied in the guinea-pig ileum. Mitragynine (1 nM - 3 μM) inhibited the ileum contraction elicited by electrical stimulation, and its pD2 value was 6.91 ± 0.04 (n = 5). Morphine (1 nM − 1 μM) also inhibited the electrically stimulated contraction in a concentration-dependent manner (pD2 7.68 ± 0.11; n = 5). Mitragynine was 10 fold less potent than morphine. Mitragynine (3–10 μM) did not show any effect on the smooth muscle contraction induced by acetylcholine or histamine. Naloxone (10–300 nM) reversed the inhibitory effect of mitragynine on electrically stimulated contraction. Furthermore, naloxone showed a shift of concentration-response curve of mitragynine to the right. There was no significant difference in the affinity of naloxone (i.e. pA2) in the presence of mitragynine or morphine. Mitragynine (3–10 μM) inhibited the naloxone-precipitated withdrawal contraction following a brief (5 min) exposure of the ileum to morphine. Tetrodotoxin (1 μM) and atropine (1 μM) inhibited the withdrawal contraction. The present results suggest that mitragynine inhibits the electrically stimulated contraction of guinea-pig ileum through the opioid receptor.

Morphine is frequently used to treat painful episodes associated with sickle cell disease (SCD) but may fail to provide adequate analgesia in many patients. This concise review focuses on unique disease related changes in physiologic variables associated with SCD that impacts pharmacokinetics and pharmacodynamics of morphine and may contribute to the variability in analgesia. Emerging evidence suggests that the allelic variants in the genes involving the opioid (UGT2B7, OPRM1, and ABCB1 genes) and nonopioid system (COMT gene) can alter the efficacy of morphine. Am. J. Hematol., 2008. © 2007 Wiley-Liss, Inc.

Oral morphine for postoperative pain after minor pediatric surgery, while increasingly popular, is not supported by evidence. We evaluated whether oral morphine was superior to ibuprofen for at-home management of children's postoperative pain. We conducted a randomized superiority trial comparing oral morphine (0.5 mg/kg) with ibuprofen (10 mg/kg) in children 5 to 17 years of age who had undergone minor outpatient orthopedic surgery (June 2013 to September 2016). Participants took up to 8 doses of the intervention drug every 6 hours as needed for pain at home. The primary outcome was pain, according to the Faces Pain Scale - Revised, for the first dose. Secondary outcomes included additional analgesic requirements, adverse effects, unplanned health care visits and pain scores for doses 2 to 8. We analyzed data for 77 participants in each of the morphine and ibuprofen groups. Both interventions decreased pain scores with no difference in efficacy. The median difference in pain sc...

The WHO guidelines on cancer pain management recommend a sequential three-step analgesic ladder. However, conclusive data are lacking as to whether moderate pain should be treated with either step II weak opioids or low-dose step III strong opioids. In a multicenter, 28-day, open-label randomized controlled study, adults with moderate cancer pain were assigned to receive either a weak opioid or low-dose morphine. The primary outcome was the number of responder patients, defined as patients with a 20% reduction in pain intensity on the numerical rating scale. A total of 240 patients with cancer (118 in the low-dose morphine and 122 in the weak-opioid group) were included in the study. The primary outcome occurred in 88.2% of the low-dose morphine and in 57.7% of the weak-opioid group (odds risk, 6.18; 95% CI, 3.12 to 12.24; P < .001). The percentage of responder patients was higher in the low-dose morphine group, as early as at 1 week. Clinically meaningful (≥ 30%) and highly mean...

OBJECTIVE Pain after total knee arthroplasty (TKA) is severe, thus adequate pain control can be a challenge. Intrathecal morphine (ITM) provides excellent postoperative analgesia for TKA, but may have side effects. Femoral nerve block (FNB) also has been used for postoperative analgesia in TKA. We examined postoperative analgesia efficacy and side effects of ITM combined with single shot femoral nerve block (SSFNB) after TKA, over the dosage range of 0.0 to 0.3 mg. MATERIAL AND METHOD Sixty patients undergoing elective TKA received SSFNB (0.5% bupivacaine 20 ml) and spinal anesthesia with 15 mg of hyperbaric bupivacaine (0.5% Heavy Marcaine) were included in this study. They were randomized to receive ITM (0, 0.1, 0.2, and 0.3 mg). A patient-controlled analgesia (PCA) device provided additional intravenous morphine. Morphine consumption, pain score, and side effects were recorded at 0, 1, 4, 8, 12, and 24 hour postoperative. Patient satisfaction was rated at the 24-hour postoperativ...

Calming the pain is one of the most constant searches of the human race. Like many other drugs, opioid medications are pain relief medications. The term opioids encompass a class of a wide variety of drugs, both natural and alkaloid compounds derived directly from
the resin of the opium poppy (termed opiates, including morphine and heroin) as well as synthetic compounds (including oxycodone and hydromorphone). All members of the opioid drug class have agonistic effects on the mu receptor in the brain ( Pikard, Penfold and
Mazhar, 2018). Although opiates are used to control pain and relieve cough and diarrhea, they create a sense of euphoria, calmness and sedation that will cause addiction. It is known that opioids cause adverse effects, such as respiratory depression, that can lead to death. The aim of this article is to examine the commonly used opiates and their effects on psychological well-being within the framework of academic articles.

Fascia Iliaca Compartment Block (FICB) has been widely used as a postoperative analgesic adjunct to opioids for total hip arthroplasty (THA), either by the conventional infrainguinal approach or the modified proximal suprainguinal approach irrespective of any specific advantage of one over the other. This study was conducted to compare the analgesic efficacy of the two techniques of FICB for postoperative analgesia. The 40 patients scheduled for THA were recruited for Intervention (s) and randomized to receive FICB either by suprainguinal approach (group S) or infrainguinal approach (group I) for postoperative analgesia with 40 ml of 0.2% bupivacaine, in addition to postoperative patient controlled analgesia (PCA) with morphine. Visual analogue scale (VAS) and PCA morphine consumption was used to assess the postoperative pain at 3, 6, 12 and 24 hours. The primary outcome was cumulative PCA morphine consumption in 24 hours. The pain intensity as measured by VAS scores showed signific...

Background: Systematic reviews of randomized trials show that empathic care (a core component of person-centered care) and placebos can reduce chronic back pain. However, this evidence has rarely been implemented and public knowledge of empathy and placebos is limited. Objectives: We conducted a trial ('OPTICARE') in a real-life setting. The trial and its aftermath were filmed for a British Broadcasting Corporation (BBC) Horizon documentary. Methods: Eligible participants aged 18-75 years with self-reported persistent back pain (>3 months) were randomised to: (1) Control group (SC): had a standard consultation and a leaflet describing NHS recommendations for back pain. (2) Standard placebo group (SP): received a three-week course of placebo pills (2 capsules, twice a day) and a standard (5-10 minute) general practice (GP) consultation. (3) Empathy and placebo group (EP): received the same as SP treatment as the standard placebo group and a longer (15-30 minute) consultation with a doctor prompted to be highly empathetic. Self-reported changes in pain after 3 weeks were measured using the Visual Analogue Scale and the Roland Morris Disability Questionnaire. The process was filmed by Windfall Films. Results: The documentary, entitled 'The Placebo Experiment: Can My Brain Cure My Body?' was first broadcast on BBC Two in the UK on 4 October 2018. It was watched by 1.9 million people. Almost all of the 117 participants in the trial reported a reduction in pain and magnitude of placebo effects is similar in real world settings as it is in clinical trials. Conclusions: This was the largest placebo study we are aware of that was conducted with a main purpose of educating the public about placebo effects and the first known published report of a study designed for a documentary. Although the trial suffered from a number of limitations, including contamination and lack of power, it is contended that randomised trials of placebo treatments can be conducted so that they benefit and educate the public.

A method to measure cutaneous hyperalgesia to thermal stimulation in unrestrained animals is described. The testing paradigm uses an automated detection of the behavioral end-point; repeated testing does not contribute to the development of the observed hyperalgesia. Carrageenan-induced inflammation resulted in significantly shorter paw withdrawal latencies as compared to saline-treated paws and these latency changes corresponded to a decreased thermal nociceptive threshold. Both the thermal method and the Randall-Selitto mechanical method detected dose-related hyperalgesia and its blockade by either morphine or indomethacin. However, the thermal method showed greater bioassay sensitivity and allowed for the measurement of other behavioral parameters in addition to the nociceptive threshold.

Background and objective:  The Pharmacy Department at the Western General Hospital in Edinburgh prepares a topically applied product in which morphine sulphate is incorporated into Instillagel® for use in reducing pain associated with rectal and other cancers. A stability indicating method was required for assessment of the stability of this combination.Methods:  A gradient high performance liquid chromatography method was developed to assess stability and an LC-MS method was used to characterize the degradants from forced degradation of the components in the formulation.Results and discussion:  The method was found to have acceptable inter- and intra-day precisions. Under all storage conditions investigated morphine sulphate remained within 98·1% and 103·2% of the initial concentration, lidocaine hydrochloride within 96·07% and 104·9% and chlorhexidine gluconate within 97·3% and 105·5%, except for samples stored at 37 °C beyond 240 h. A sample of the admixture was stored up to 7 months at 37 °C and was found to be reasonably stable with only the chlorhexidine concentration declining appreciably to 92% of the initial concentration. Some of the degradants of chlorhexidine and morphine were characterized by liquid chromatography mass spectrometry. It could be concluded that the admixture was stable for over 22 days at 4 °C protected from light, over 22 days at 25 °C exposed to normal light, and for 7 months at 37 °C protected from light.Conclusion:  The components in the combination were found to have good long-term stability.

Although the majority of potentially preventable fatalities among U.S. combat forces serving in Afghanistan and Iraq have died from hemorrhagic shock, the majority of U.S. medics carry morphine autoinjectors for prehospital battlefield analgesia. Morphine given intramuscularly has a delayed onset of action and, like all opioids, may worsen hemorrhagic shock. Additionally, on a recent assessment of prehospital care in Afghanistan, combat medical personnel noted that Tactical Combat Casualty Care (TCCC) battlefield analgesia recommendations need to be simplified--there are too many options and not enough clear guidance on which medication to use in specific situations. They also reported that ketamine is presently being used as a battlefield analgesic by some medics in theater with good results. This report proposes that battlefield analgesia be achieved using one or more of three options: (1) the meloxicam and Tylenol in the TCCC Combat Pill Pack for casualties with relatively minor pain who are still able to function as effective combatants; (2) oral transmucosal fentanyl citrate (OTFC) for casualties who have moderate to severe pain, but who are not in hemorrhagic shock or respiratory distress and are not at significant risk for developing either condition; or (3) ketamine for casualties who have moderate to severe pain but who are in hemorrhagic shock or respiratory distress or are at significant risk for developing either condition. Ketamine may also be used to increase analgesic effect for casualties who have previously been given opioids (morphine or fentanyl.).