Search Results (125)

This literature review, in light of the presented case report, explores the complex interplay between gabapentin (GBP), a gamma-aminobutyric acid (GABA) analog, and the hypothalamic–pituitary–adrenal (HPA) axis in patients undergoing major surgical procedures. It specifically investigates the potential impact of GBP on cortisol levels, stress responses, and infection risk, illustrated by a detailed clinical case. This review combines a comprehensive literature search with a case report of a 17-year-old male with osteosarcoma who experienced transient adrenal insufficiency and infections while receiving GBP. The case is analyzed in the context of the existing literature on GBP and the HPA axis. The findings highlight the intricate relationship between GBP use, adrenal insufficiency, and infection susceptibility. It underscores the need for further research and clinical vigilance when prescribing GBP to patients with underlying medical conditions, particularly in the context of major surgical procedures. The review underscores the need for further research and clinical vigilance when prescribing GBP, particularly in perioperative settings. In conclusion, GBP’s effects on the HPA axis and immune responses are complex and multifaceted. Clinicians should exercise caution when prescribing GBP, especially for patients with underlying conditions undergoing major surgery. Further research is needed to elucidate the mechanisms of GBP’s influence on cortisol levels and stress responses. Full article

Background: Despite widespread consensus on the need to reduce benzodiazepine (BZD) use in older adults, prescription rates in the U.S. have paradoxically increased over the past few decades. Objective: We examined (1) the characteristics of the BZD adverse reaction cases in patients aged 50 and older that were admitted to a healthcare facility (HCF) and experienced major effects/death, and (2) the associations between the concomitant use of opioids and/or antidepressants and HCF admission and major effects/death among BZD cases. Methods: We used the 2015–2022 National Poison Data System (NPDS), which contained data from 55 America’s Poison Centers. We fitted two multivariable logistic regression models to examine the associations between the co-use of opioids and/or antidepressants and HCF admission and major effects/death. Results: Of the BZD cases that were examined (N = 1979), 14.9% or 295 cases were admitted to healthcare facilities, and 8.5% of those who were followed up (77 out of 893 cases) experienced major effects or death. The number of co-used substances, co-use of opioids and antidepressants, atypical antipsychotics, anticonvulsants, muscle relaxants, and Gabapentin were associated with greater odds of healthcare admission. Co-use of opioids and healthcare admission were associated with greater odds of major effects/death. Conclusions: Adverse reactions and healthcare admissions are likely to be prevented when healthcare providers limit and carefully monitor BZD prescribing, especially for those who are on other medications, including prescription opioids and antidepressants. Full article

Introduction: Cannabis sativa L. (CSL) extract has pain-relieving potential due to its cannabinoid content, so the effects of two CSL extracts on alleviating neuropathic pain were investigated in vivo. Methods and groups: Male Wistar rats (n = 130) were divided into groups and received vincristine (0.1 mg/kg) and gabapentin (60 mg/kg) to induce and relieve neuropathic pain or CSL extracts (D and B). The mRNA and protein expression of the cannabinoid receptors type 1 and 2 (CB1R, CB2R) were evaluated in the cerebral cortex, hippocampus, and lymphocytes. Behavioural tests (Tail-Flick and von Frey) were performed on all animals. Results: VK-induced neuropathic pain was accompanied by decreased CB1R protein level and CB2R mRNA expression in the cortex. Gabapentin relieved pain and increased CB1R protein levels in the hippocampus compared to the vincristine group. Hippocampus CB1R protein expression increased with the administration of extract D (10 mg/kg, 40 mg/kg) and extract B (7.5 mg/kg, 10 mg/kg) compared to VK group. In the cerebral cortex CSL decreased CB1R protein expression (10 mg/kg, 20 mg/kg, 40 mg/kg of extract B) and mRNA level (5 mg/kg, 7.5 mg/kg of extract B; 20 mg/kg of extract D) compared to the VK-group.CB2R protein expression increased in the hippocampus after treatment with extract B (7.5 mg/kg) compared to the VK-group. In the cerebral cortex extract B (10 mg/kg, 20 mg/kg) increased CB2R protein expression compared to VK-group. Conclusion: Alterations in cannabinoid receptor expression do not fully account for the observed behavioural changes in rats. Therefore, additional signalling pathways may contribute to the initiation and transmission of neuropathic pain. The Cannabis extracts tested demonstrated antinociceptive effects comparable to gabapentin, highlighting the antinociceptive properties of Cannabis extracts for human use. Full article

Introduction: Although opiate narcotics may worsen gastroparesis(GP), patients can take these for abdominal pain (AP) or other chronic pain syndromes. This study aims to evaluate medications patients with gastroparesis use for AP and compare patients who use opiate analgesics for AP to those using opiate analgesics for non-abdominal pain. Methods: Patients at a tertiary academic center gastroenterology clinic completed the Patient Assessment of Gastrointestinal Disorders–Symptom Severity Index (PAGI-SYM) and Quality of Life Short-Form 8 (QOL SF-8) surveys between 10/2021 and 03/2023. Patients recorded gastroparesis treatments, pain treatments and indication, and any hospitalizations/emergency department (ED) visits within 3 months of a clinic visit. Results: A total of 53 patients were enrolled: 72% reported having AP. Patients were using the following medications for AP: 25% heating pad, ice or hot showers, 20.8% acetaminophen, 14.6% hyoscyamine, 13% opiate use, 13% marijuana use, 10.4% dicyclomine, 8.3% Nonsteroidal anti-inflammatory drugs (NSAIDs), 4% benzodiazepine, and 2.1% gabapentin. The reported reasons for using opiates were 58% AP, 16.6% chronic back pain, 16.6% Reflex Sympathetic Dystrophy (RSD) and fibromyalgia, and 8.3% osteoarthritis. All opiate users reported daily scheduled use. AP severity scores (4.1 vs. 2.8; p = 0.041), morphine equivalent usage (77 ± 44 vs. 32 ± 28; p = 0.037), and the number of ER visits (1.0 vs. 0 over 3 months) were higher in patients using opiates for AP than those using opiates for non-abdominal pain. Conclusions: In this series, 72% of patients with gastroparesis had abdominal pain, and 13% of patients were taking opiates. Patients who used opiate analgesics for abdominal pain had a higher average abdominal pain severity score and used a higher amount of opiate analgesia than patients using opiates for musculoskeletal pain. Abdominal pain in patients with gastroparesis can be harder to control with opiate analgesia compared to non-abdominal pain, supporting the concept of avoiding chronic opiate usage for abdominal pain in gastroparesis. Full article

Inhibition of soluble epoxide hydrolase (sEH) is a promising therapeutic strategy for treating neuropathic pain. These inhibitors effectively reduce diabetic neuropathic pain and inflammation induced by Freund’s adjuvant which makes them a suitable alternative to traditional opioids. This study showcased the notable analgesic effects of compound AMHDU (1,1′-(hexane-1,6-diyl)bis(3-((adamantan-1-yl)methyl)urea)) in both inflammatory and diabetic neuropathy models. While lacking anti-inflammatory properties in a paw edema model, AMHDU is comparable to celecoxib as an analgesic in 30 mg/kg dose administrated by intraperitoneal injection. In a diabetic tactile allodynia model, AMHDU showed a prominent analgesic activity in 10 mg/kg intraperitoneal dose (p < 0.05). The effect is comparable to that of gabapentin, but without the risk of dependence due to a different mechanism of action. Low acute oral toxicity (>2000 mg/kg) and a high therapeutic index makes AMHDU a promising candidate for further structure optimization and preclinical evaluation. Full article

Peripheral neuropathy (PN) is a multifaceted disorder characterised by peripheral nerve damage, manifesting in symptoms like pain, weakness, and autonomic dysfunction. This review assesses preclinical models in PN research, evaluating their relevance to human disease and their role in therapeutic development. The Streptozotocin (STZ)-induced diabetic rat model is widely used to simulate diabetic neuropathy but has limitations in faithfully replicating disease onset and progression. Cisplatin-induced PN models are suitable for studying chemotherapy-induced peripheral neuropathy (CIPN) and closely resemble human pathology. However, they may not fully replicate the spectrum of sensory and motor deficits. Paclitaxel-induced models also contribute to understanding CIPN mechanisms and testing neuroprotective agents. Surgical or trauma-induced models offer insights into nerve regeneration and repair strategies. Medications such as gabapentin, pregabalin, duloxetine, and fluoxetine have demonstrated promise in these models, enhancing our understanding of their therapeutic efficacy. Despite progress, developing models that accurately mirror human PN remains imperative due to its complex nature. Continuous refinement and innovative approaches are critical for effective drug discovery. This review underscores the strengths and limitations of current models and advocates for an integrated approach to address the complexities of PN better and optimise treatment outcomes. Full article

Background: Postoperative pain remains a significant challenge after knee and hip surgeries, two of the most frequently performed procedures, preventing patients from seeking timely surgical help. Gabapentinoids, gabapentin, and pregabalin, have been gaining attention in postoperative pain management. Methods: We conducted a meta-analysis to evaluate the efficacy of gabapentinoids in pain management after knee and hip surgery. PubMed, Scopus, and Cochrane Library were searched for relevant randomized controlled trials (RCTs) published before January 2023. Results: Fifteen articles reporting 1320 patients were analyzed. Cumulative pain intensity at rest and on movement was lower in the experimental group with the mean difference (MD) = −0.30 [−0.55,−0.05], p-value = 0.02, and MD = −0.41 [−0.68,−0.13], p-value = 0.004, respectively. However, the difference was not clinically meaningful and lacked statistical significance at each time period. The gabapentinoid group required less opioid consumption in morphine equivalents (MD = −6.42 [−9.07, −3.78] mg, p-value < 0.001). There was a lower incidence of postoperative nausea in the experimental group with a risk ratio (RR) of 0.69 [0.55, 0.86], p-value < 0.001. A subgroup analysis showed that gabapentinoids reduced pain on movement on postoperative day two after total knee arthroplasty but not hip arthroplasty. There was insufficient data to examine the efficacy of gabapentinoids in the reduction of chronic postoperative pain in knee/hip surgery. Conclusions: Thus, gabapentinoids were associated with a reduction in postoperative pain intensity at rest and on movement, morphine consumption, and the incidence of postoperative nausea in the early postoperative period following knee and hip surgeries. However, pain reduction was not clinically relevant. Sedation has not been evaluated in this work and, if performed, this may have influenced the conclusions. An important limitation of this study is that different gabapentinoids, their administration times and dosages, as well as varying intraoperative management protocols, were pooled together. Full article

Objectives: Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes mellitus (DM) with symptoms like intense pain and impaired quality of life. This condition has no treatment; instead, the pain is managed with various antidepressants, including duloxetine. The aim of this study is to analyze the evidence on the efficacy of duloxetine in the management of DPN. Methods: A systematic search in different databases was conducted using the keywords “diabetic neuropathy”, “duloxetine therapy”, “neuropathic pain”, and “Diabetes Mellitus”. Finally, eight studies were included in this meta-analysis. Results: All articles comparing duloxetine at different doses vs. a placebo reported significant differences in favor of duloxetine on pain scales like 24 h Average Pain Severity (standardized mean difference [SMD] = −1.06, confidence interval [CI] = −1.09 to −1.03, and p < 0.00001) and BPI Severity (SMD = −0.70, CI = −0.72 to −0.68, and p < 0.00001), among others. A total of 75% of the meta-analyses of studies comparing duloxetine at different doses showed a tendency in favor of the 120 mg/d dose. There were significant differences in favor of duloxetine when compared to routine care on the Euro Quality of Life (SMD = −0.04, CI = −0.04 to −0.03, and p < 0.00001) and SF-36 Survey (SMD = −5.86, CI = −6.28 to −5.44, and p < 0.00001) scales. There were no significant differences on the visual analog scale (VAS) when comparing duloxetine and gabapentin. Conclusions: Duloxetine appears to be effective in the management of DPN in different pain, symptom improvement, and quality of life scales. Full article

As sex-gender differences have been described in the responses of patients to certain medications, we hypothesized that the responses to medications recommended for neuropathic pain may differ between men and women. We conducted a literature review to identify articles reporting potential sex-gender differences in the efficacy and safety of these medications. Only a limited number of studies investigated potential sex-gender differences. Our results show that women seem to achieve higher blood concentrations than men during treatment with amitriptyline, nortriptyline, duloxetine, venlafaxine, and pregabalin. Compared to men, higher rates of women develop side effects during treatment with gabapentin, lidocaine, and tramadol. Globally, the sex-gender differences would suggest initially administering smaller doses of these medications to women with neuropathic pain compared to those administered to men. However, most of these differences have been revealed by studies focused on the treatment of other diseases (e.g., depression). Studies focused on neuropathic pain have overlooked potential sex-gender differences in patient responses to medications. Despite the fact that up to 60% of patients with neuropathic pain fail to achieve an adequate response to medications, the potential role of sex-gender differences in the efficacy and safety of pharmacotherapy has not adequately been investigated. Targeted studies should be implemented to facilitate personalized treatments for neuropathic pain. Full article

This prospective, randomized study aimed to assess the anxiolytic efficacy of gabapentin or alprazolam in cats during short-term postoperative hospitalization. Sixty cats were randomly assigned to three groups (gabapentin-treated [100 mg per cat], alprazolam-treated [0.125 mg per cat], or placebo-treated), with treatments administered twice daily for two days. Stress levels were evaluated using Cat Stress Scores, serum cortisol, and glucose concentrations. Pain scores, food consumption, and adverse effects such as sedation were also monitored. Fifty-five cats completed the study. Both medications demonstrated similar reductions in stress levels. Cats receiving gabapentin had lower pain scores, while those receiving alprazolam exhibited significantly increased food intake on the first postoperative day. However, both medications resulted in comparable levels of sedation. In the context of postoperative hospitalization, pharmacological intervention with anxiolytics could be effective in reducing stress levels. Despite potential side effects, gabapentin and alprazolam may contribute to an improved quality of short-term hospitalization for cats. Full article

Background and Objectives: Gabapentin has shown promise as a potential agent for the treatment of alcohol withdrawal syndrome. We aimed to evaluate the effectiveness of gabapentin as a benzodiazepine-sparing agent in patients undergoing alcohol withdrawal treatment in all the hospitals of a large tertiary healthcare system. Materials and Methods: Medical records of patients admitted to the hospital for alcohol withdrawal management between 1 January 2020 and 31 August 2022 were reviewed. Patients were divided into two cohorts: benzodiazepine-only treatment who received benzodiazepines as the primary pharmacotherapy and gabapentin adjunctive treatment who received gabapentin in addition to benzodiazepines. The outcomes assessed included the total benzodiazepine dosage administered during the treatment and the length of hospital stay. The statistical models were calibrated to account for various factors. Results: A total of 4364 patients were included in the final analysis. Among these, 79 patients (1.8%) received gabapentin in addition to benzodiazepines, and 4285 patients (98.2%) received benzodiazepines only. Patients administered gabapentin required significantly lower average cumulative benzodiazepine dosages, approximately 17.9% less, compared to those not receiving gabapentin (median 2 mg vs. 4 mg of lorazepam equivalent dose (p < 0.01)). However, there were no significant differences in outcomes between the two groups. Conclusions: Our findings demonstrate that using gabapentin with benzodiazepine was associated with a reduction in the cumulative benzodiazepine dosage for alcohol withdrawal. Considering gabapentin as an adjunctive therapy holds promise for patients with comorbidities who could benefit from reducing benzodiazepine dose. This strategy warrants further investigation. Full article

The use of gabapentin in treating dogs with behavioral disorders is not well described. To characterize behavioral effects of gabapentin, this study surveyed 50 owners whose dogs were prescribed gabapentin at a veterinary behavior-focused practice over a five-year period. Most owners (72%) reported that gabapentin was moderately or very effective at improving their dog’s behavior. The majority of owners reported at least one side effect (70%), with sedation being the most common. Sedation was more likely to be seen at doses higher than 30 mg/kg. Specific dose ranges (mg/kg) did not correlate with any other reports of side effects nor effectiveness. Dogs with a diagnosis of conflict-related aggression were more likely to have owners report that gabapentin was effective at improving behavior compared to dogs with other behavioral diagnoses (p = 0.04), while dogs diagnosed with aggression secondary to high arousal were less likely to have owners report that gabapentin was effective (p = 0.01). Overall, reports of effect varied widely and, with the exception of sedation, did not correlate with specific mg/kg dose ranges. Results suggest that some dogs may be more sensitive or resistant to adverse and/or therapeutic effects than others and multiple dosage trials may be needed before finding the best fit. Full article

Gabapentin (GBP) was originally developed as a potential agonist for Gamma-Amino-Butyric-Acid (GABA) receptors, aiming to inhibit the activation of pain-signaling neurons. Contrary to initial expectations, it does not bind to GABA receptors. Instead, it exhibits several distinct pharmacological activities, including: (1) binding to the alpha-2-delta protein subunit of voltage-gated calcium channels in the central nervous system, thereby blocking the excitatory influx of calcium; (2) reducing the expression and phosphorylation of CaMKII via modulation of ERK1/2 phosphorylation; (3) inhibiting glutamate release and interfering with the activation of NMDA receptors; (4) enhancing GABA synthesis; (5) increasing cell-surface expression of δGABA_A receptors, contributing to its antinociceptive, anticonvulsant, and anxiolytic-like effects. Additionally, GBP displays (6) inhibition of NF-kB activation and subsequent production of inflammatory cytokines, and (7) stimulation of the purinergic adenosine A1 receptor, which supports its anti-inflammatory and wound-healing properties. Initially approved for treating seizures and postherpetic neuralgia, GBP is now broadly used for various conditions, including psychiatric disorders, acute and chronic neuropathic pain, and sleep disturbances. Recently, as an eye drop formulation, it has also been explored as a therapeutic option for ocular surface discomfort in conditions such as dry eye, neurotrophic keratitis, corneal ulcers, and neuropathic ocular pain. This review aims to summarize the evidence supporting the molecular effects of GBP, with a special emphasis on its applications in ocular surface diseases. Full article

Chronic postsurgical pain (CPSP) following total knee arthroplasty (TKA) and total hip arthroplasty (THA) is a prevalent complication of joint replacement surgery which has the potential to decrease patient satisfaction, increase financial burden, and lead to long-term disability. The identification of risk factors for CPSP following TKA and THA is challenging but essential for targeted preventative therapy. Recent meta-analyses and individual studies highlight associations between elevated state anxiety, depression scores, preoperative pain, diabetes, sleep disturbances, and various other factors with an increased risk of CPSP, with differences observed in prevalence between TKA and THA. While the etiology of CPSP is not fully understood, several factors such as chronic inflammation and preoperative central sensitization have been identified. Other potential mechanisms include genetic factors (e.g., catechol-O-methyltransferase (COMT) and potassium inwardly rectifying channel subfamily J member 6 (KCNJ6) genes), lipid markers, and psychological risk factors (anxiety and depression). With regards to therapeutics and prevention, multimodal pharmacological analgesia, emphasizing nonopioid analgesics like acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), has gained prominence over epidural analgesia. Nerve blocks and local infiltrative anesthesia have shown mixed results in preventing CPSP. Ketamine, an N-methyl-D-aspartate (NMDA)-receptor antagonist, exhibits antihyperalgesic properties, but its efficacy in reducing CPSP is inconclusive. Lidocaine, an amide-type local anesthetic, shows tentative positive effects on CPSP. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) have mixed results, while gabapentinoids, like gabapentin and pregabalin, present hopeful data but require further research, especially in the context of TKA and THA, to justify their use for CPSP prevention. Full article

The goal of this review is to shed light on the management of orofacial discomfort after a cancer diagnosis in the head and neck region. A search was conducted on PubMed, Scopus, and Web of Science to identify studies on postoperative pain control in oral cancer. The review included open-access research, investigations into pain management, randomized clinical trials, retrospective studies, case-control studies, prospective studies, English-written studies, and full-text publications. Exclusion criteria included animal studies; in vitro studies; off-topic studies; reviews, case reports, letters, or comments; and non-English language. Three reviewers independently accessed databases and assigned a quality rating to the chosen articles. The review explores postoperative pain management in oral cancer patients; highlighting persistent opioid use; the efficacy of adjuvant drugs, such as gabapentin; and a multimodal approach. It emphasizes the need for personalized pain management, recognizing individual pain perception and tailoring interventions. Integrating pharmacological and non-pharmacological strategies is crucial for comprehensive pain management. The review also serves as a guide for future research, emphasizing the need for standardized methodologies and diverse participant populations. Full article