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Background: Gabapentinoids increasingly utilized for neuropathic pain, possibly to curb opioid prescribing. At the same time, data suggest subsequent increases in misuse and overdose of gabapentinoids, often in mixed overdoses. We sought to determine national trends and characteristics of gabapentinoid prescribing, including co-use with opioids, from the emergency department (ED)., Methods: This is a retrospective review of the National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2012 to 2021. Our primary outcome was the trend in ED visits in which gabapentinoids were prescribed at discharge. Secondarily, we identified trends in gabapentinoid and opioid co-prescribing and gabapentin and pregabalin prescribing at ED discharge. We examined demographic data and used descriptive statistics, Shapiro Wilke's test, Pearson's Spearman's rho (SR) or Pearson's correlation coefficient (PC) as applicable. Neural networks were used to identify the most important predictors of opioid utilization during the same visit., Results: Between 2012 and 2021, there were an estimated 7,242,694 (0.53% of all ED visits) visits in which gabapentinoids were prescribed at ED discharge. Prescriptions increased from a total of 138,479 (0.1%) in 2012 to 893,495 (0.63%) in 2021 (PC: 0.85, p < 0.001). Opioids were co-prescribed in 27.2% of all visits in which gabapentinoids were prescribed, with no change over time (PC: -0.47, p = 0.09). Pregabalin prescription increased linearly over time (PC: 0.64, p = 0.02). The most important predictors of opioid administration or co-prescribing were whether an alternative provider (e.g., consult or nurse practitioner) saw the patient (100%), insurance (94.4%), age (75.9%), and region (75.2%)., Conclusion: Despite an association of misuse and overdose, often associated with opioids, gabapentinoids were increasingly prescribed at ED discharge. While these agents may be safer alternatives to opioids, misuse may be an associated consequence of increased prescribing, which warrants further investigation., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the relationship between sociodemographic, clinical, and neurophysiological variables and health-related quality of life (HR-QOL) of patients with phantom limb pain (PLP)., Methods: This is a cross-sectional analysis of a previous clinical trial. Univariate and multivariate linear and logistic regression analyses were used to model the predictors of HR-QOL. We utilized a sequential modeling approach with increasing adjustment levels, controlling for age and sex, and other relevant clinical variables (time since amputation, level of amputation, and pain). HR-QOL was assessed by the SF-36 Health Survey and its 8 subdomains., Results: We analyzed baseline data from 92 patients with lower-limb amputations. They were mostly male (63%), 45.2 ± 15.6 years, with a mean time since amputation of 82.7 ± 122.4 months, and an overall SF-36 score of 55.9 ± 21.5. We found an association between intracortical facilitation (ICF) in the affected hemisphere, gabapentin usage, and HR-QOL. ICF is a predictor of better HRQOL, whereas gabapentin usage was associated with a poorer HR-QOL, with the main model explaining 13.4% of the variance in the outcome. For the SF-36 subdomains, ICF was also a positive predictor for social functioning, bodily pain, and vitality, while medication usage was associated with lower scores in mental health, general health perception, bodily pain, and vitality., Conclusion: We found firsthand 2 new independent predictors of HR-QOL in individuals with PLP, namely, the neurophysiological metric ICF and gabapentin usage. These results highlight the role of the motor cortex excitability in the HR-QOL and stress the need for treatments that favor the neuroplastic adaptation after amputation, for which ICF may be used as a possible marker., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Masticatory myositis is an autoimmune neuromuscular disorder that affects the muscles of mastication. The affected individual has difficulties in opening or closing the mouth, pain, and swelling in the acute phase, and significant atrophy of the affected musculature in the chronic phase. A guinea pig ( Cavia porcellus ) with a history of chronic hyporexia, recurrent cheek teeth overgrowth, and loss of facial silhouette, was suspected of having masticatory myositis. The disease was confirmed by computed tomography and histopathological examination of muscle fragments. The patient was treated with a protocol involving corticosteroids and gabapentin, and occlusal correction procedures., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: For ophthalmic patients, eye discomfort is a major problem that requires efficient pain treatment techniques. Pregabalin and gabapentin have surfaced as viable treatments for post-refractive surgery pain. To manage pain after refractive surgery, gabapentin and pregabalin were evaluated in this systematic review and meta-analysis., Methodology: A thorough search of databases including PubMed, Embase, Cochrane Library, and CINAHL was performed until March 2024. Inclusion criteria were randomized controlled trials assessing pregabalin and/or gabapentin's effectiveness in treating pain post-PRK, LASIK, and LASEK surgeries., Results: Six studies met inclusion criteria, comprising a total of 391 patients undergoing various corneal surgeries. The meta-analysis revealed that pregabalin was significantly more effective than placebo in reducing pain on the first and second postoperative days (SMD day 1: -0.32, 95% CI -0.54, -0.09; SMD day 2: -0.55, 95% CI -0.85, -0.25), while gabapentin showed significant pain reduction on the second day only (SMD day 2: -0.42, 95% CI -0.71, -0.13). Combined analysis for both medications showed significant pain reduction on the first- and second-days post-surgery. No significant increase in adverse events was associated with either medication. Publication bias was minimal except for a slight asymmetry noted on day 1 effectiveness., Conclusion: Pregabalin and gabapentin are effective in reducing postoperative pain following refractive surgeries, with pregabalin showing a greater effect. Both medications are safe, with no significant increase in adverse events. Further research with standardized methodologies and long-term follow-up is recommended to optimize postoperative pain management in ocular surgeries., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Few studies report outcomes for enhanced recovery pathways in ambulatory anorectal surgery. We hypothesize that an ambulatory anorectal enhanced recovery pathway with multimodal analgesia can reduce postoperative opioid use., Objective: To compare postoperative opioid use in patients undergoing ambulatory anorectal surgery who receive multimodal analgesia versus standard of care without multimodal analgesia., Design: A prospective randomized trial of patients undergoing elective anal fistula or hemorrhoid surgery from September 2018 to May 2022., Setting: Urban teaching hospital., Patients: Adults aged 18 to 70 years undergoing elective anal fistula or hemorrhoid surgery from September 2018 to May 2022., Intervention: Multimodal enhanced recovery pathway including preoperative and postoperative nonopioid analgesia with oral acetaminophen, gabapentin, and ketolorac., Main Outcome Measures: Primary end point was oral opioid use during the first postoperative week. Secondary end points included maximum pain and nausea scores, adverse events, and emergency room or hospital admissions during the first 30 days postoperatively., Results: Of the 109 enrolled patients, 20 were lost to follow-up. The remaining 89 patients had a median age of 38 years (range, 20-67) and included 41 women (46%). There were no significant differences between the enhanced recovery protocol arm and non-enhanced recovery protocol arm in terms of preoperative and surgical characteristics. The primary end point of this study, that is, oral morphine milligram equivalents use during the first week, was significantly higher among patients in the non-enhanced recovery protocol arm (79 mg; range, 0-600) than patients in the enhanced recovery protocol arm (8 mg; range, 0-390; p = 0.002). On subgroup analysis, both fistula and hemorrhoid surgery patients assigned to the non-enhanced recovery protocol arm took significantly higher oral morphine milligram equivalents in the first week than patients in the enhanced recovery protocol arm. There was no significant difference in secondary end points., Limitations: Patients and providers were not blinded. Our findings are limited to hemorrhoid and fistula surgery and may not be applicable to other anorectal procedures., Conclusions: Enhanced recovery protocols including multimodal analgesia should be used in elective anal fistula and hemorrhoid surgery to decrease postoperative opioid use. See the Video Abstract ., Clinical Trial Registration: ClinicalTrials.gov ID NCT03738904., Implementacin De Protocolo De Recuperacin Acelerada Multimodal En Ciruga Anorrectal Ambulatoria Un Estudio Aleatorizado: ANTECEDENTES:Pocos estudios reportan resultados de programas de recuperación acelerada en la cirugía anorrectal ambulatoria. Presumimos que un programa anorrectal ambulatorio de recuperación acelerada con analgesia multimodal puede reducir el uso posoperatorio de opioides.OBJETIVO:Comparar el uso posoperatorio de opioides en pacientes sometidos a cirugía anorrectal ambulatoria que reciben analgesia multimodal versus atención estándar sin analgesia multimodal.DISEÑO:Un estudio prospectivo aleatorizado de pacientes sometidos a cirugía electiva de fístula anal o hemorroides desde septiembre de 2018 hasta mayo de 2022.LUGAR: Hospital universitario urbano.PACIENTES:Adultos de 18 a 70 años sometidos a cirugía electiva de fístula anal o hemorroides desde septiembre de 2018 hasta mayo de 2022.INTERVENCIÓN:Programa de recuperación acelerada multimodal que incluye analgesia no opioide pre y posoperatoria con paracetamol oral, gabapentina y ketoloraco.PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue el uso de opioides orales durante la primera semana postoperatoria. Los resultados secundarios incluyeron puntuaciones máximas de dolor y náuseas, eventos adversos e ingresos a la sala de emergencias o al hospital durante los primeros 30 días después de la operación.RESULTADOS:De los 109 pacientes incluidos, 20 se perdieron durante el seguimiento. Los 89 pacientes restantes tenían una mediana de edad de 38 (rango, 20-67) años e incluían 41 (46%) mujeres. No hubo diferencias significativas entre los grupos del protocolo de recuperación acelerada (Grupo E) y del protocolo de recuperación no acelerada (Grupo NE) en términos de características preoperatorias y quirúrgicas. El resultado principal del estudio, el uso de MME oral durante la primera semana, fue significativamente mayor entre los pacientes del grupo NE (79 mg; rango: 0-600) que los pacientes del grupo E (8 mg; rango: 0-390) ( p = 0,002). En el análisis de subgrupos, los pacientes de cirugía de fístula y hemorroides asignados al grupo NE tomaron MME oral significativamente más alto en la primera semana que los pacientes del grupo E. No hubo diferencias significativas en los resultados secundarios.LIMITACIONES:Los pacientes y proveedores no fueron cegados. Nuestros hallazgos se limitan a la cirugía de hemorroides y fístulas y pueden no ser aplicables a otros procedimientos anorrectales.CONCLUSIONES:Se deben utilizar protocolos de recuperación acelerada que incluyan analgesia multimodal en la cirugía electiva de fístula anal y hemorroides para disminuir el uso posoperatorio de opioides. (Traducción- Dr. Francisco M. Abarca-Rendon )CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov ID NCT03738904., (Copyright © The ASCRS 2024.)

Cold atmospheric plasma (CAP) has been employed as a therapy against both acute and chronic skin lesions, contaminated or not, and has effects on angiogenesis and reepithelialization promoting healing. In this context, the present study aimed to evaluate the effects of a CAP jet associated with pharmacological treatment described by the 2015 AAHA/AAFP pain management guidelines and the 2022 WSAVA guidelines for the recognition, assessment, and treatment of pain, on the healing of chronic skin lesions caused by a pruritic reaction resulting from post-surgical neuropathic pain. To this end, a single CAP application was performed on a feline patient with a 6 months old recurrent contaminated cervical skin lesions along with administration of ketamine (10 µg/kg/min) following the prescription of prednisone (1 mg/kg, SID, 6 days), gabapentin (8 mg/kg, BID, 60 days) and amitriptyline (0.5 mg /kg, SID, 60 days). A single application of plasma associated with an NMDA antagonist, anti-inflammatory steroid, tricyclic antidepressant and gabapentinoid thus provided a significant improvement in the macroscopic appearance of the lesion within 10 days, and the owner reported the cessation of intense itching within the first four hours after treatment and a consequent improvement in the animal's quality of life. The medical treatment was finished almost a year since the writing of this paper, without clinical or reported recurrent signs of the condition. Therefore, we observed that single dose CAP application associated with ketamine, gabapentin, amitriptyline and prednisone leads to significant healing of chronically infected skin lesions resulting from post-surgical neuropathic pain., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: The effect of individual non-narcotic analgesics in cystectomy enhanced recovery after surgery (ERAS) is unknown. Additionally, many non-narcotic medications are associated with side effects pertinent to the cystectomy population. To better understand the actual use and utility of these medications, we sought to characterize the association between non-narcotic medications and milligram morphine equivalent (MME) narcotic score during the postoperative inpatient stay., Methods: We reviewed 260 consecutive ERAS cystectomy patients. The MME impact of non-narcotic compliance and cumulative dose of medication received was evaluated separately with general linear models. We also assessed relationship of non-narcotic compliance to patient reported pain score, length of stay (LOS), and time to return of bowel function (ROBF) and performed manual review of postoperative documentation to identify reasons for medication noncompliance., Results: Compliance with postoperative acetaminophen, gabapentin, and ketorolac was low. There was an inverse relationship between ketorolac dose and MME on postoperative day 1 (-0.026 MME/mg; P = 0.004) and postoperative day 2 (-0.33 MME/mg; P < 0.001). Compliance with ketorolac was associated with lower MME on postoperative day 1 (26.1 MME v. 33.6 MME; P = 0.023). There were no such associations identified with gabapentin or acetaminophen. Gabapentin compliance was associated with earlier ROBF (3.7 days v. 4.3 days; P = 0.006). Ketorolac compliance was associated with lower pain score on POD1 (3.25 VAS v. 4.07 VAS; P = 0.019) and POD2 (3.05 VAS v. 3.85 VAS; P = 0.040) There was no association between medication compliance and LOS. The most common reasons identified for non-compliance with gabapentin and ketorolac were renal function concerns (38% and 40% respectively), bleeding concerns with ketorolac (20%) and concerns for neurologic adverse effect with gabapentin (16%)., Conclusion: Compliance with non-narcotic medications in our ERAS cystectomy protocol was poor. There was a modest association with ketorolac and postoperative MME but no association with gabapentin or acetaminophen. Further study will clarify the role of these medications for cystectomy patients. Component specific analysis of protocolized care is valuable and may alter care pathways., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: The ERAS protocol is a set of international guidelines established to expedite patients' discharge after colorectal surgery. It does this by aiming to prevent postoperative complications early, and return the patient to normal function allowing earlier discharge. Complications such as PONV, DVT, ileus and pain are common after surgery to name a few, and delay discharge. Early treatment and prevention of these complications however is suggested to aid a patients' return to home at earlier rates than traditional practice., Methods: A prospective chart review and questionnaire was performed on patients undergoing colorectal surgery in UHL in a 6-month period from February to September 2023. Patients were approached on the 3rd day postoperatively and informed about the project. Exclusion criteria included patients who went to HDU or ICU postoperatively., Results: In total, 33 patients were recruited. A target of greater than 70% compliance was reached for a variety of the elements of the ERAS protocol such as laparoscopic surgery, preoperative assessments, nutritional drinks, LMWH, oral intake within 24 h of surgery, and intraoperative antiemetics. Unsatisfactory compliance was found with documentation of postoperative antibiotics use of preoperative gabapentin., Conclusion: UHL has a satisfactory compliance of over 70% with a large variety of elements of the ERAS protocol. Areas of improvement required include postoperative antibiotic and preoperative gabapentin usage. With the collective effort of the multidisciplinary team, along with education, the ERAS protocol can successfully be applied and implemented in a model 4 hospital in Ireland., (© 2024. The Author(s).)

Clinical appointment generates stress in feline patients, influencing the frequency of veterinary care with the species. The purpose of this study was to assess serum cortisol in cats submitted to oral gabapentin and integrative practices during clinical care. Twenty cats were evaluated in three clinical appointments, one week apart. All cats were submitted to treatments: placebo (PL), gabapentin (GA), and integrative practices (IP) (music therapy, pheromone therapy, and chromotherapy). GA and PL were administered by the owners 90 min before transportation to the veterinary teaching hospital, and IP were applied 30 min before clinical care. Cats were physically examined at all timepoints, and blood samples were collected for cortisol measurement. Serum cortisol levels ranged from 0.49 µg/dL to 17.99 µg/dL. Mean cortisol concentrations when cats received PL (7.6 µg/dL) were higher than when cats received GA (4.9 µg/dL) and IP (4.1 µg/dL). There was a statistical difference in cortisol levels when cats receiving PL and GA were compared (p = 0.03) and between PL and IP (p = 0.005). The study showed that feline serum cortisol levels were lower when cats received the treatments to IP (integrative practices) and GA (gabapentin), demonstrating that these are applicable methods for reducing stress of feline patients in clinical evaluation., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Abstract: Growing evidence from pharmacovigilance data and postmortem toxicology reports highlights the misuse potential of gabapentinoids. This study aimed to investigate the risk of serious adverse outcomes (drug misuse, overdose, major trauma), and their risk factors, in primary care patients who are prescribed gabapentinoids. Using the UK Clinical Practice Research Datalink, a matched cohort study calculated adverse event rates separately for gabapentinoid-exposed and unexposed cohorts. In the exposed cohort, event rates for exposure to a range of potential risk factors were calculated. Event rates were compared using Cox proportional hazards models, adjusted for age, sex, deprivation, previous mental health diagnosis, and coprescribing with potentially interacting medicines. Substance misuse (gabapentin adjusted hazard ratio [95% CI]: 2.40 [2.25-2.55]), overdose (2.99 [2.56-3.49]), and major trauma (0-2.5 years: 1.35 [1.28-1.42]; 2.5 to 10 years: 1.73 [1.56-1.95]) were more common among patients prescribed gabapentinoids than matched individuals who were not. The association with overdose was stronger for pregabalin than gabapentin. All adverse outcomes were significantly associated with smoking, history of substance misuse, overdose, or a mental health condition and prescription of opioids, benzodiazepines, antidepressants, and Z-drug hypnotics (eg, gabapentin hazard ratios for association of concurrent opioid use: misuse 1.49 [1.47-1.51]; overdose 1.87 [1.78-1.96]; major trauma 1.28 [1.26-1.30]). Our findings highlight the importance of careful patient selection when prescribing gabapentinoids and the need to educate prescribers about the risks of these drugs, particularly in combination with other central nervous system depressants., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Background: Healthcare providers may be utilizing central nervous system (CNS) depressants to reduce opioid use due to recent changes in public policy. Combination use of these agents with opioids increases the risk of respiratory depression and death. Healthcare expenditures by individuals using these drug combinations have not been previously quantified. We sought to characterize healthcare costs and expenditures associated with a population reporting concurrent CNS depressants and opioid use compared with nonopioid analgesics in the United States from 2009 to 2019., Methods: A serial cross-sectional design was used to compare the healthcare expenditures of adult Medical Expenditure Panel Survey respondents who were prescribed nonopioid analgesics, opioids only, opioids/benzodiazepines (BZD), opioids/BZD/skeletal muscle relaxants (SMR), or opioids/gabapentin (gaba) using pooled data from 2009 to 2019. Expenditure (cost and resource utilization) categories included inpatient, outpatient, office-based, and prescription medicine. Average marginal effects were used to compare survey-weighted annual costs and resource utilizations across the groups as compared to nonopioid analgesic respondents, adjusted for covariates., Results: A weighted total of 34 241 838 individuals were identified. Most were opioid-only respondents (46.5%), followed by nonopioid analgesic (43.4%), opioid/BZD (5.3%), opioid-gaba (3.5%), and opioid/BZD/SMR respondents (1.3%). In comparison to the study groups with nonopioid analgesics, opioid-gaba users had the highest significant incremental cost difference among the different pairings (+$11 684, P  < .001). Opioid-gaba, opioid/BZD, and opioid/BZD/SMR respondents had significantly higher inpatient, emergency department, and prescription drug costs and use compared to nonopioid analgesic respondents. Opioid-only respondents had higher outpatient and office-based costs and visits compared to nonopioid analgesic respondents., Conclusions: As healthcare providers seek to utilize fewer opioids for pain management, attention must be paid to ensuring safe and effective use of concurrent CNS depressants to mitigate high healthcare costs and burden., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Explore the indications for long-stay gabapentin use and elucidate the factors spurring the rapid increase in gabapentin prescribing in nursing homes (NHs)., Methods: National cross-sectional survey of NH prescribers distributed anonymously using SurveyMonkey. Sampling for convenience was obtained through crowdsourcing, leveraging collaborations with NH clinician organizations. Developed by a multidisciplinary team, pilot data/existing literature informed survey content., Results: A total of 131 surveys completed. Participants: 71% white, 52% female, 71% physicians. Off-label gabapentin prescribing was ubiquitous. Nearly every clinician used gabapentin for neuropathic pain, most for any form of pain. Many clinicians also prescribe gabapentin to moderate psychiatric symptoms and behaviors. Clinicians' prescribing was influenced by opioid, antipsychotic, and anxiolytic reduction policies because gabapentin was perceived as an unmonitored and safer alternative., Conclusions: Off-label gabapentin increases are closely linked to opioid reduction efforts as more NH clinicians utilize gabapentin as an unmonitored opioid alternative. Our results highlight, however, the less recognized significance of long-stay prescribing for psychiatric symptoms and the similar contribution of psychotropic reduction initiatives, a phenomenon warranting further scrutiny., Clinical Implications: Clinicians perceive gabapentin as safer than the drugs it is replacing. Whether this is true remains unclear; the individual- and population-level risks of increased gabapentin use are largely unknown.

Background: Prurigo nodularis (PN) is a pruritic skin disease characterized by multiple intensely itchy skin nodules in symmetrically distributed areas of the extremities. There are limited studies on the epidemiology and treatment pathways of PN, especially moderate-to-severe PN, from England., Objectives: To assess the epidemiology and treatment pathways of mild and moderate-to-severe PN in England., Methods: This retrospective cohort study used data from the Clinical Practice Research Datalink and Hospital Episode Statistics in England. Adult patients (aged ≥ 18 years) with a PN-specific diagnosis code allocated any time between 1 April 2007 and 1 March 2019 (patient identification period) were selected. Patients were included if their first PN diagnostic code (index diagnosis date; IDD) was recorded during the identification period, with data available 6 months before and ≥ 12 months after the IDD. Patients were classified as having moderate-to-severe PN (MSPN) or mild PN (MiPN), based on the presence or absence of a prescription record, post-IDD, for either a systemic immunosuppressant or a gabapentinoid. Patients with MSPN and MiPN were matched 1 : 1 according to age, sex and IDD. Prevalence and incidence were calculated for each year from 2007 to 2019. Drugs prescribed post-IDD were analysed., Results: A total of 8933 patients (MSPN, n = 2498; MiPN, n = 6435) were included in the study; 2462 patients with MiPN and 2462 with MSPN were included for the comparative analysis. The presence of atopic dermatitis, asthma and eosinophilic oesophagitis were significantly higher (all P < 0.001) in patients with MSPN compared with those with MiPN. The overall prevalence of cases of PN increased during the study period. The incidence rate also showed a similar trend. The rates of prescription of potent and super-potent topical corticosteroids (TCS), topical calcineurin inhibitors, first- and second-generation antihistamines, oral and injectable systemic corticosteroids, methotrexate, antidepressants and tacrolimus were significantly higher (all P < 0.001) in patients with MSPN compared with those with MiPN., Conclusions: The epidemiology of PN was consistent with that found in other European studies. Patients with MSPN received a significantly higher number of prescriptions for potent TCS and systemic drugs compared with patients with MiPN., Competing Interests: Conflicts of interest D.B., R.H., R.M. and O.D. are employees of and may hold stock options in Sanofi. O.B. was an employee of Sanofi UK when the study was conducted and the manuscript written. E.M., B.H. and E.H. are employees of Human Data Sciences and received funding from Sanofi. A.B. is an employee of Barts Health NHS Trust and Queen Mary University, and has provided ad hoc consultancy for Sanofi, AbbVie, Almirall, Sanofi, UCB, Lilly, Novartis, Galderma, LEO Pharma and Janssen for work submitted outside the conduct of this study., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Neuropathy is a disturbance of function or a pathological change in nerves causing poor health and quality of life. A proportion of chronic pain patients in the community suffer persistent neuropathic pain symptoms because current drug therapies may be suboptimal so there is a need for new therapeutic modalities. This study investigated the neuroprotective flavonoid, 6-methoxyflavone (6MF), as a potential therapeutic agent and gabapentin as the standard comparator, against neuropathic models. Thus, neuropathic-like states were induced in Sprague-Dawley rats using sciatic nerve chronic constriction injury (CCI) mononeuropathy and systemic administration of streptozotocin (STZ) to induce polyneuropathy. Subsequent behaviors reflecting allodynia, hyperalgesia, and vulvodynia were assessed and any possible motoric side-effects were evaluated including locomotor activity, as well as rotarod discoordination and gait disruption. 6MF (25-75 mg/kg) antagonized neuropathic-like nociceptive behaviors including static- (pressure) and dynamic- (light brushing) hindpaw allodynia plus heat/cold and pressure hyperalgesia in the CCI and STZ models. 6MF also reduced static and dynamic components of vulvodynia in the STZ induced polyneuropathy model. Additionally, 6MF reversed CCI and STZ suppression of locomotor activity and rotarod discoordination, suggesting a beneficial activity on motor side effects, in contrast to gabapentin. Hence, 6MF possesses anti-neuropathic-like activity not only against different nociceptive modalities but also impairment of motoric side effects., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose of Review: Mirogabalin is a novel gabapentinoid medication for the treatment of neuropathic pain. The purpose of this review is to discuss current evidence for its use. Gabapentinoids are widely prescribed for neuropathic pain. Mirogabalin offers theoretical advantages over traditional gabapentinoids due to its specificity for the α2δ-1 subunit of voltage-gated calcium channels. It is theorised that this specificity may reduce adverse drug reactions by minimising binding to the α2δ-2 subunit which is responsible for many of the gabapentinoid side effects., Recent Findings: Mirogabalin's slower dissociation from the α2δ-1 compared with α2δ-2, and its higher potency may also impart an efficacy benefit over traditional gabapentinoids. These theoretical advantages of mirogabalin remain inconclusive in clinical practice, with mixed evidence regarding mirogabalin versus traditional gabapentinoids. Some studies suggest a reduced side effect profile yet, others fail to demonstrate significant differences. Regarding efficacy, mirogabalin may be superior to placebo for several neuropathic pain syndromes, but evidence of widespread benefit over traditional gabapentinoids is currently lacking., Summary: Mirogabalin offers theoretical promise, but large, independent studies are required to further assess its performance versus traditional gabapentinoids., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Gabapentin is often used as an analgesic after rotator cuff repair surgery and is recommended as an additional analgesic for arthroscopic rotator cuff repairs. However, evidence of its effects on biological healing mechanisms is lacking. The objective of this study was to investigate the potential of gabapentin in improving tendon-to-bone healing after rotator cuff repair using a rat model., Materials and Methods: A total of 20 male rats were randomly allocated to one of two groups: group 1 (repair only, n=10) or group 2 (gabapentin injection, n=10). The rats in the experimental group (group 2) were administered 80 mg/kg of gabapentin subcutaneously 30 minutes before surgery, followed by 80 mg/kg subcutaneously every 24 hours for 48 hours. We used the left shoulder of every rat, while for biomechanical analysis, we used the right shoulder., Results: There was no significant difference in the load to failure, ultimate stress, or elongation between the groups. Collagen continuity, orientation, and density were better in group 2 than group 1., Conclusion: In a rat model of rotator cuff repair, gabapentin had a positive impact on the quality of collagen organization at the junction between the tendon and bone, while preserving the biomechanical properties. We propose the use of gabapentin as a supplementary analgesic agent for postoperative pain relief after arthroscopic rotator cuff repair; however, further studies of the effect of gabapentin on biological healing mechanisms are required. [ Orthopedics . 2024;47(5):e241-e246.].

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) affects patients' quality of life and treatment effectiveness. Gabapentinoids, like gabapentin and pregabalin, are often used for CIPN treatment, but their efficacy and safety remain uncertain. This study reviews and analyses randomised controlled trial data on this topic., Materials/methods: We searched PubMed, Embase and Cochrane CENTRAL until 29 August 2022 for studies on gabapentinoid use in CIPN. Meta-analysis was performed using RevMan V.5.4 and the Metafor package in R. Outcomes included pain scores, quality of life and adverse drug events., Results: For the prevention setting, our meta-analysis shows that pregabalin did not significantly improve average pain (standardised mean difference (SMD) -0.14, 95% CI -0.51 to 0.23; I 2 =26% (95% CI 0% to >98%)) or quality of life (mean difference (MD) 2.5, 95% CI -4.67 to 9.67; p=0.49) in preventing CIPN compared with placebo. However, it showed a potential trend towards reducing the worst pain (SMD -0.28, 95% CI -0.57 to 0.01; I 2 =0% (95% CI 0% to 98%; p=0.06)). For the treatment setting, some studies have shown a potential therapeutic effect of gabapentinoids. However, the results are not consistent between studies. Given the studies' heterogeneity, a meta-analysis in treatment setting was not performed., Conclusion: There is limited evidence to support the use of gabapentinoids in CIPN. In prevention setting, gabapentinoids do not significantly prevent CIPN. In treatment setting, studies have been inconsistent in their conclusions, lacking definitive benefits over placebo. More comprehensive and higher quality research is needed in the future., Prospero Registration Number: CRD42022361193., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To explore cancer survivors' historical and current use of analgesics for chronic chemotherapy-induced peripheral neuropathy (CIPN)., Sample & Setting: 142 post-treatment cancer survivors who received neurotoxic chemotherapy and were experiencing moderate to severe CIPN., Methods & Variables: Participants completed the Treatment-Induced Neuropathy Assessment Scale at baseline and reported all analgesics used to manage CIPN. Frequency of historical or current prescription analgesic use for chronic CIPN was described and stratified by CIPN pain severity., Results: At baseline, 31% of participants reported historical use of analgesics for CIPN and 46% of participants were currently using analgesics for CIPN. Gabapentin was the most frequently used analgesic, historically (20%) and currently (34%), and duloxetine was used less frequently (6% historical use, 10% current use). Many participants with severe pain (59%) reported using analgesics for CIPN., Implications for Nursing: Duloxetine, the first-line treatment for chronic CIPN pain, was used less frequently than gabapentin, a common prescription analgesic for neuropathic pain. Further research is needed to determine strategies to promote the implementation of evidence-based CIPN treatments in clinical practice.

Pain is a common public health problem and remains as an unmet medical need. Currently available analgesics usually have limited efficacy or are accompanied by many adverse side effects. To achieve satisfactory pain relief by multimodal analgesia, new combinations of nefopam and gabapentinoids (pregabalin/gabapentin) were designed and assessed in inflammatory, osteoarthritis and neuropathic pain. Isobolographic analysis was performed to analyze the interactions between nefopam and gabapentinoids in carrageenan-induced inflammatory pain, mono-iodoacetate-induced osteoarthritis pain and paclitaxel-induced peripheral neuropathic pain in mice. The anti-inflammatory effect and motor performance of monotherapy or their combinations were evaluated in the carrageenan-induced inflammatory responses and rotarod test, respectively. Nefopam (1, 3, 5, 10, 30 mg/kg, p.o.), pregabalin (3, 6, 12, 24 mg/kg, p.o.) or gabapentin (25, 50, 75, 100 mg/kg, p.o.) dose-dependently reversed mechanical allodynia in three pain models. Isobolographic analysis indicated that the combinations of nefopam and gabapentinoids exerted synergistic anti-nociceptive effects in inflammatory, osteoarthritis, and neuropathic pain mouse models, as evidenced by the experimental ED 50 (median effective dose) falling below the predicted additive line. Moreover, the combination of nefopam-pregabalin/gabapentin alleviated carrageenan-induced inflammation and edema, and also prevented gabapentinoids-related sedation or ataxia by lowering their effective doses. Collectively, the co-administration of nefopam and gabapentinoids showed synergistic analgesic effects and may result in improved therapeutic benefits for treating pain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Benign prostatic hyperplasia (BPH) is a common chronic disease affecting the health of the urinary system and the quality of life in older adults. Plasmakinetic resection of the prostate (PKRP) is one of the important surgical procedures for treating BPH; However, older adults may experience anesthesia complications and postoperative pain. This retrospective study aimed to assess the effects of preoperative oral gabapentin on anesthesia outcomes in older adults with BPH undergoing PKRP and to provide detailed clinical evidence for improving the impact of surgical treatment., Methods: The medical records of 178 older adults with BPH who underwent PKRP in Tianjin Hospital from March 2021 to March 2023 were retrospectively analyzed. After excluding 18 patients who did not meet the inclusion criteria, 160 patients were finally included in the study. According to preoperative use of gabapentin, patients were divided into the observation group (n = 75, received gabapentin) and the control group (n = 85, did not receive gabapentin). The baseline data, visual analog scale (VAS) scores, postoperative Ramsay Sedation Scale (RSS) scores, and incidence of adverse reactions were collected., Results: There were no significant differences observed between the two groups in terms of age, body mass index, prostate volume, surgery duration, International Prostate Symptom Score (IPSS), American Society of Anesthesiologists (ASA) classification, history of hypertension and diabetes mellitus, VAS scores at postoperative 36 hours and 48 hours, and RSS scores at postoperative 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, and 48 hours ( p > 0.05). Compared to the control group, the observation group had significantly lower VAS scores at postoperative 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours ( p < 0.001), and the incidence of adverse reactions was significantly lower within 24 hours after surgery ( p < 0.05)., Conclusions: Preoperative administration of gabapentin before PKRP could reduce pain severity and the incidence of adverse reactions and improve anesthetic effects in older adults with BPH, which is conducive to postoperative recovery., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s).)

Abstract: The pressing need for safer, more efficacious analgesics is felt worldwide. Preclinical tests in animal models of painful conditions represent one of the earliest checkpoints novel therapeutics must negotiate before consideration for human use. Traditionally, the pain status of laboratory animals has been inferred from evoked nociceptive assays that measure their responses to noxious stimuli. The disconnect between how pain is tested in laboratory animals and how it is experienced by humans may in part explain the shortcomings of current pain medications and highlights a need for refinement. Here, we survey human patients with chronic pain who assert that everyday aspects of life, such as cleaning and leaving the house, are affected by their ongoing level of pain. Accordingly, we test the impact of painful conditions on an ethological behavior of mice, digging. Stable digging behavior was observed over time in naive mice of both sexes. By contrast, deficits in digging were seen after acute knee inflammation. The analgesia conferred by meloxicam and gabapentin was compared in the monosodium iodoacetate knee osteoarthritis model, with meloxicam more effectively ameliorating digging deficits, in line with human patients finding meloxicam more effective. Finally, in a visceral pain model, the decrease in digging behavior correlated with the extent of disease. Ultimately, we make a case for adopting ethological assays, such as digging, in studies of pain in laboratory animals, which we believe to be more representative of the human experience of pain and thus valuable in assessing clinical potential of novel analgesics in animals., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Objectives: To investigate the efficacy and safety of pulsed radiofrequency of the dorsal root ganglion combined with ozone injection for treating acute herpes zoster (HZ) neuralgia in middle-aged and elderly adults., Methods: A total of 164 middle-aged and elderly patients with acute HZ were randomly assigned to 2 groups: the pulsed radiofrequency combined with ozone injection group (group A) and the pulsed radiofrequency group (group B). The therapeutic effects were evaluated using Numeric Rating Scale (NRS) scores and the average doses of gabapentin (mg/d) preoperatively and 1 day, 2 weeks, 4 weeks, 12 weeks, and 24 weeks postoperatively. The incidence of clinically significant postherpetic neuralgia (PHN) and complications in the 2 groups were recorded., Results: The data showed that the NRS scores and the doses of gabapentin after treatment were significantly lower when compared with the baseline values in both groups. Compared with group B, the NRS scores and the doses of postoperative gabapentin were significantly lower in group A. The incidence of PHN was significantly lower at weeks 4, 12, and 24 in group A than in group B. No adverse reactions occurred in either of the 2 groups post-treatment., Conclusions: The results indicated that ozone injection in the dorsal root ganglion combined with pulsed radiofrequency therapy was more effective in treating acute HZ neuralgia in middle-aged and elderly adults. It provides patients with longer-lasting pain relief, decreased incidence of PHN and the doses of medication, and improved quality of life than with Pulsed Radiofrequency treatment., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Practice guidelines recommend nonpharmacologic and nonopioid therapies as first-line pain treatment for acute pain. However, little is known about their utilization generally and among individuals with opioid use disorder (OUD) for whom opioid and other pharmacologic therapies carry greater risk of harm., Objective: To determine the association between a pre-existing OUD diagnosis and treatment of acute low back pain (aLBP)., Design: Retrospective cohort study using 2016-2019 Medicare data., Participants: Fee-for-service Medicare beneficiaries with a new episode of aLBP., Main Measures: The main independent variable was OUD diagnosis measured prior to the first LBP claim (i.e., index date). Using multivariable logistic regressions, we assessed the following outcomes measured within 30 days of the index date: (1) nonpharmacologic therapies (physical therapy and/or chiropractic care), and (2) prescription opioids. Among opioid recipients, we further assessed opioid dose and co-prescription of gabapentin. Analyses were conducted overall and stratified by receipt of physical therapy, chiropractic care, opioid fills, or gabapentin fills during the 6 months before the index date., Key Results: We identified 1,263,188 beneficiaries with aLBP, of whom 3.0% had OUD. Two-thirds (65.8%) did not receive pain treatments of interest at baseline. Overall, nonpharmacologic therapy receipt was less prevalent and opioid and nonopioid pharmacologic therapies were more common among beneficiaries with OUD than those without OUD. Beneficiaries with OUD had lower odds of receiving nonpharmacologic therapies (aOR = 0.62, 99%CI = 0.58-0.65) and higher odds of prescription opioid receipt (aOR = 2.24, 99%CI = 2.17-2.32). OUD also was significantly associated with increased odds of opioid doses ≥ 90 morphine milligram equivalents/day (aOR = 2.43, 99%CI = 2.30-2.56) and co-prescription of gabapentin (aOR = 1.15, 99%CI = 1.09-1.22). Similar associations were observed in stratified groups though magnitudes differed., Conclusions: Medicare beneficiaries with aLBP and OUD underutilized nonpharmacologic pain therapies and commonly received opioids at high doses and with gabapentin. Complementing the promulgation of practice guidelines with implementation science could improve the uptake of evidence-based nonpharmacologic therapies for aLBP., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Objective: Understanding the clinical and demographic profile of patients on gabapentinoids can highlight areas of prescribing disparities, inform clinical practice, and guide future research to optimize effectiveness and safety of gabapentinoids for pain management. We used a national sample of Medicare beneficiaries to examine trends, patterns, and patient-level predictors of gabapentinoid use among long-term opioid users., Methods: Using a national Medicare sample between 2014 and 2020, we examined factors associated with gabapentinoid use among long-term opioid users. We included Medicare eligible long-term opioid users with no prior gabapentinoid use. The primary outcome was gabapentinoid use after the long-term opioid use episode. Logistic regression was used to test the association with gabapentinoid use for year, age, sex, race/ethnicity, region, Medicare entitlement, low-income status, frailty, pain locations, anxiety, depression, opioid use disorder, and opioid morphine milligrams equivalent., Results: Gabapentinoid use among long-term opioid users increased from 12.6% in 2014 to 16.8% in 2019 (p < .0001). Factors associated with increased gabapentinoid use were Hispanic ethnicity, back pain, nerve pain, and moderate or high opioid usage. Factors associated with decreased gabapentinoid use were older age and Medicare entitlement due to old age., Conclusions: Variation of gabapentinoid use by socio-demographics and insurance status indicates opportunities to improve pain management and a need for shared therapeutic decision making informed by discussion between pain patients and providers regarding safety and effectiveness of pain therapies. Our findings underscore the need for future research into the comparative effectiveness and safety of gabapentinoids for non-cancer chronic pain in various subpopulations., Competing Interests: Declaration of competing interest The authors have no financial, personal, or other potential conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Fibromyalgia, a chronic pain disorder, impacts approximately 2% of adults in the US. Gabapentin and pregabalin are common treatments to manage fibromyalgia-related pain. Our recent study showed the risk of adverse cardiovascular events increased in diabetic neuropathy patients who were prescribed gabapentin or pregabalin. Here, we investigated whether the prescription of gabapentin or pregabalin has similar cardiovascular risk in patients with fibromyalgia., Methods: This retrospective cohort study leveraged electronic health records from 64 US healthcare organizations with 112 million patients. The study population included 105,602 patients first diagnosed with fibromyalgia and followed by a prescription of gabapentin, pregabalin, or other FDA-approved drugs for treating fibromyalgia from 2010 to 2019. Outcomes were deep venous thrombosis (DVT), myocardial infarcts (MI), peripheral vascular disease (PVD), strokes, heart failure, and pulmonary embolism (PE). In propensity-score-matched cohorts, 1-year and 5-year hazard ratios (HRs) were computed with their respective 95% confidence intervals (CIs). Additionally, we conducted sensitivity analyses on the subpopulations without other possible indications., Results: For 5-year follow-up, gabapentin increased the risk of PVD (HR = 1.46, 95% CI = 1.17-1.80), MI (HR = 1.31, 95% CI = 1.03-1.66), heart failure (HR = 1.27, 95% CI = 1.10-1.48), DVT (HR = 1.80, 95% CI = 1.33-2.44), and PE (HR = 2.23, 95% CI = 1.62-3.07). Pregabalin increased the risk of DVT (HR = 1.49, 95% CI = 1.01-2.20), and PE (HR = 2.24, 95% CI = 1.43-3.50). For 1-year follow-up, gabapentin increased the risk of PVD (HR = 1.32, 95% CI = 1.11-1.57), DVT (HR = 1.35, 95% CI = 1.09-1.68), and PE (HR = 1.36, 95% CI = 1.17-1.57). Pregabalin increased the risk of PVD (HR = 1.32, 95% CI = 1.06-1.63) and PE (HR = 1.25, 95% CI = 1.03-1.52). Sensitivity analyses showed similar trends., Conclusion: In fibromyalgia patients, the prescription of gabapentin and pregabalin moderately increased the risk of several adverse cardiovascular events. This risk, together with benefits and other adverse reactions, should be considered when prescribing these medications for fibromyalgia patients., Competing Interests: RPB holds a patent on the idea that indicators of fluid retention can be used to assess the cardiovascular risk of a medication. YP, DCK, and RX do not have competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Pan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We purposed to explore the consequences of the use quercetin and fisetin alone and in combination with pregabalin and gabapentin, which are used in the management of neuropathic pain, and on neuropathic pain in general. The anti-allodynic effect of various doses (5, 10, and 20 mg/kg) of quercetin and fisetin, both singly and in combination with pregabalin and gabapentin, was evaluated by developing a neuropathic pain model induced by chronic constrictive nerve damage in rats. The effectiveness of these flavonoids was investigated by combining them with gabapentin (50 mg/kg) and pregabalin (15 mg/kg), choosing the effectual dose of 10 mg/kg and the dose of 5 mg/kg, which did not show significant antiallodynic effects. In groups combined with gabapentin and pregabalin, it was determined that they showed a significant antiallodynic effect compared with 50 mg/kg gabapentin and 15 mg/kg pregabalin. In conclusion, in our combination studies, it was observed that the effectiveness of gabapentin and pregabalin, was increased and the duration of effect was prolonged when used with lower doses of flavonoids. Based on these findings; it is possible to say that quercetin and fisetin are potential agents that can be used alone or in combination with other effective treatments to alleviate neuropathic pain., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Lance-Adams syndrome is a rare and debilitating disorder characterized by successful cardiopulmonary resuscitation resulting in myoclonus activity. Alcohol withdrawal seizures from alcohol use disorder may further exacerbate Lance-Adams syndrome. We aim to present a case of Lance-Adams syndrome complicated by alcohol withdrawal seizures and successfully treated with a combination of valproate, clonazepam, and gabapentin., Materials and Methods: The patient's electronic medical record, direct patient care experiences, and a comprehensive literature search were used for this case report. We report a 41-year-old male patient with Lance-Adams syndrome with concurrent alcohol use disorder. Treatment was improved when adding gabapentin for alcohol use disorder treatment, alongside combination antiepileptic therapy. A PubMed search was conducted to examine Lance-Adams syndrome case reports of successful combination antiepileptic therapy, with a secondary evaluation of patients with concurrent alcohol use disorder., Results: The literature search yielded 18 articles, which resulted in 21 individual cases in which combination antiepileptic drug therapy was successful in treating myoclonus secondary to Lance-Adams syndrome; however, none of the case reports utilized gabapentin synergistically. One case described Lance-Adams syndrome complicated by alcohol consumption and similar to our patient, the patient used alcohol to abolish myoclonic activity., Conclusions: To the best of our knowledge, this is the first case report documenting a patient with Lance-Adams syndrome and concurrent alcohol use disorder, with a positive effect of gabapentin use. Gabapentin, when used for alcohol use disorder treatment, may be an appropriate adjunct agent in the management of patients receiving combination antiepileptic therapy for the treatment of Lance-Adams syndrome., Competing Interests: Conflicts of Interest and Source of Funding: The authors have no conflicts of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: A single administration of the opioid receptor antagonist methocinnamox (MCAM) antagonizes the antinociceptive effects of µ-opioid receptor agonists for 2 weeks or longer. Such a long duration of antagonism could necessitate the use of nonopioid drugs for treating pain in patients receiving MCAM for opioid use disorder (OUD)., Methods: The antinociceptive effects of fentanyl and nonopioid drugs were assessed in 24 male Sprague Dawley rats using a complete Freund's adjuvant (CFA) model of inflammatory pain. Twelve rats received 10mg/kg MCAM and 12 received vehicle; half (n=6) of the animals from each treatment group were treated (intraplantar) with CFA or saline. Hypersensitivity to mechanical stimulation was measured using a von Frey anesthesiometer. Fentanyl (0.01-0.1mg/kg), ketamine (17.8-56mg/kg), gabapentin (32-100mg/kg), meloxicam (3.2-10mg/kg), and ∆ 9 -tetrahydrocannabinol (THC, 1-10mg/kg) were administered intraperitoneally and tested every 3 days in a pseudorandom order. Next, the same drugs were studied for effects on motor performance using a rotarod apparatus., Results: CFA-induced hypersensitivity was attenuated by fentanyl in vehicle- but not MCAM-treated rats. THC, ketamine, and gabapentin attenuated (up to 82, 66, and 46 %, respectively) CFA-evoked mechanical hypersensitivity in both MCAM- and vehicle-treated rats. Meloxicam failed to alter CFA-evoked mechanical hypersensitivity in either group. Fentanyl, THC, gabapentin, and meloxicam did not affect motor performance in either group whereas ketamine impaired motor performance in both groups (up to 71 % reduction in latency to fall)., Conclusions: These data suggest that ketamine, gabapentin, and THC could be effective for treating inflammatory pain under conditions of long term µ-opioid receptor antagonism., Competing Interests: Declaration of Competing Interest CPF is co-holder of a US Patent for methocinnamox (MCAM). Other authors have no declarations of interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

We examine the cost-effectiveness of treating epilepsy with anti-epileptic medicines in autistic children, looking at impacts on healthcare providers (in England, Ireland, Italy and Spain) and children's families (in Ireland). We find carbamazepine to be the most cost-effective drug to try first in children with newly diagnosed focal seizures. For England and Spain, oxcarbazepine is the most cost-effective treatment when taken as additional treatment for those children whose response to monotherapy is suboptimal. In Ireland and Italy, gabapentin is the most cost-effective option. Our additional scenario analysis presents the aggregate cost to families with autistic children who are being treated for epilepsy: this cost is considerably higher than healthcare provider expenditure., (© 2023. The Author(s).)

Introduction: Gabapentin has been used in enhanced recovery after surgery (ERAS) pathways for pain control for patients undergoing ambulatory uro-oncologic surgery; however, it may cause undesirable side effects. We studied the causal association between gabapentin and rapidity of recovery and perioperative pain management after minimally invasive uro-oncologic surgery., Methods: We identified 2397 patients ≤ 65 years undergoing prostatectomies or nephrectomies between 2018 and 2022; 131 (5.5%) did not receive gabapentin. We tested the effect of gabapentin use on time of discharge and perioperative opioid consumption, respectively, using multivariable linear regression adjusting for potential confounders including age, gender, BMI, American Society of Anesthesiologists score, and surgery type., Results: On adjusted analysis, we found no evidence of a difference in discharge time among those who did vs did not receive gabapentin (adjusted difference 0.07 hours shorter on gabapentin; 95% CI -0.17, 0.31; P = .6). There was no evidence of a difference in intraoperative opioid consumption by gabapentin receipt (adjusted difference -1.5 morphine milligram equivalents; 95% CI -4.2, 1.1; P = .3) or probability of being in the top quartile of postoperative opioid consumption within 24 hours (adjusted difference 4.2%; 95% CI -4.8%, 13%; P = .4). We saw no important differences in confounders by gabapentin receipt suggesting causal conclusions are justified., Conclusions: Our confidence intervals did not include clinically meaningful benefits from gabapentin, when used with an ERAS protocol, in terms of length of stay or perioperative opioid use. These results support the omission of gabapentin from ERAS protocols for minimally invasive uro-oncologic surgeries.

Objective: This study aimed to systematically evaluate the clinical efficacy of gabapentin and pregabalin in the treatment of acute herpes zoster (HZ) neuralgia, including pain control and the occurrence of adverse effects., Methods: A systematic computerized search was conducted in October 2023 in PubMed, Embase, Web of Science, Cochrane Library, VIP, CNKI, and Wanfang databases. Data from randomized controlled trials (RCTs) comparing gabapentin analogs for the treatment of acute HZ neuralgia were searched. Endpoints were visual analog scores (Visual Analog Scale) and adverse effects at 1, 2, and 4 weeks. Data from studies that met the inclusion criteria were extracted for meta-analysis and sensitivity analysis using Revman 5.4 and Stata16., Results: The study included 292 patients from 6 RCTs. Of these, 118 were in the gabapentin-treated group, 37 were in the pregabalin-treated group, and 137 were in the placebo-controlled group. The gabapentin group showed superior pain reduction compared with the placebo group ( P < 0.05), but adverse events were more frequent., Conclusion: Gabapentin can effectively reduce acute HZ neuralgia in patients. Pregabalin requires additional RCTs to supplement the analysis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Although gabapentin has been increasingly prescribed to older adults, the relation between gabapentin initiation and longer-term neurocognitive changes is not well understood. Thus, this study aimed to examine the association of gabapentin initiation with cognitive and motor function decline in older adult participants with cognitive impairment., Methods: A retrospective cohort study was conducted using the National Alzheimer's Coordinating Center Uniform Data Set (2005-March 2023). Participants with cognitive impairment at the visit of gabapentin initiation (i.e., index visit) were included. Using the incidence density sampling method, up to nine non-users were randomly selected for each initiator. Cognitive decline over 1 year was defined as any increase in Clinical Dementia Rating global score (CDR ® GLOB) or a 1-point increase in CDR ® sum of boxes (CDR ® SB). Functional status decline over 1 year was defined as at least a 3-point increase in the Functional Activities Questionnaire (FAQ) sum or a 0.3-point increase of mean of FAQ. Motoric decline over 1 year was defined as new clinician reports of gait disorder, falls, and slowness. To mitigate confounding and selection bias, joint stabilized inverse probability of treatment weights and censoring weights were used. Analyses compared index with index + 1 and index + 2 visits., Results: For the study of cognitive and functional status decline, we included 505 initiators (mean age [SD] 78.8 [7.4]; male = 45%) and 4545 non-users (79.2 [7.6]; 50.1%). For the study of motor decline, we included 353 initiators (78.3 [7.2]; 42.8%) and 3177 non-users (78.5 [7.4]; 48.1%). Gabapentin initiation was not statistically associated with decline on CDR ® GLOB, CDR ® SB, FAQ sum, or mean FAQ at the index + 1 or index + 2 visits. However, gabapentin initiation was significantly associated with increased odds of new falls at the index + 2 visit (odds ratio [95% confidence interval] 2.5 [1.3, 4.6])., Conclusions: Over 1 or 2 years of follow-up, gabapentin initiation was not associated with decline in cognitive or functional status but was associated with increased odds of falling among research participants with cognitive impairment., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction / Objectives: Stressful events like earthquakes might worsen the symptoms of fibromyalgia, although the influence of medications on these consequences is yet uncertain. The objective of this study was to examine the influence of an earthquake on the symptoms of fibromyalgia and evaluate the impacts of medications used to treat fibromyalgia on the clinical picture., Method: Ninety-five fibromyalgia patients were enrolled in a comparative study and divided into two groups: medication and non-medication. Three subcategories of medication groups were established: selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and gabapentinoid drugs (GDs). Before and after the earthquake, clinical evaluations were conducted using the Fibromyalgia Impact Questionnaire (FIQ), Hospital Anxiety and Depression Scale (HADS), and Jenkins Sleep Rating Scale (JSS). Statistical analyses were conducted to compare the scores before and after the earthquake and evaluate the differences between the groups., Results: Statistically significant increases were observed in FIQ, HADS-anxiety, HADS-depression, and JSS scores in the medication and non-medication groups before and after the earthquake comparisons (p < 0.05). Non-medication group reported significantly higher post-earthquake changes in FIQ, HADS-anxiety, HADS-depression, and JSS compared to the medication group (p < 0.05). While HADS-anxiety, HADS-depression, and JSS changes after the earthquake differed according to the drug subgroups (p < 0.05), no statistically significant difference was observed in FIQ values (p > 0.05). The highest scores were detected in the GD subgroup., Conclusions: This study highlights the substantial impact of earthquakes on fibromyalgia patients. Medication use may assist in reducing the detrimental effects of stresses like earthquakes on fibromyalgia symptomatology. Future research with larger sample sizes and more extended follow-up periods is needed to explain these findings and optimize treatment regimens for fibromyalgia patients experiencing significant stressors., (© 2024. The Author(s).)

Background: Gabapentin supplementation may have some potential in pain control after lumbar laminectomy and discectomy, and this meta-analysis aims to explore the impact of gabapentin supplementation on postoperative pain management for lumbar laminectomy and discectomy., Methods: PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched, and we included randomized controlled trials assessing the effect of gabapentin supplementation on the pain control of lumbar laminectomy and discectomy., Results: Five randomized controlled trials were finally included in the meta-analysis. Overall, compared with control intervention for lumbar laminectomy and discectomy, gabapentin supplementation was associated with significantly lower pain scores at 2 hours (MD = -2.75; 95% CI = -3.09 to -2.41; P < .00001), pain scores at 4 hours (MD = -2.28; 95% CI = -3.36 to -1.20; P < .0001), pain scores at 24 hours (MD = -0.70; 95% CI = -0.86 to -0.55; P < .00001) and anxiety score compared to control intervention (MD = -1.32; 95% CI = -1.53 to -1.11; P < .00001), but showed no obvious impact on pain scores at 12 hours (MD = -0.58; 95% CI = -1.39 to 0.22; P = .16). In addition, gabapentin supplementation could significantly decrease the incidence of vomiting in relative to control intervention (OR = 0.31; 95% CI = 0.12-0.81; P = .02), but they had similar incidence of nausea (OR = 0.51; 95% CI = 0.15-1.73; P = .28)., Conclusions: Gabapentin supplementation benefits to pain control after lumbar laminectomy and discectomy., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Long-term opioid prescription to manage chronic non-cancer pain (CNCP) is rapidly rising, despite the lacking evidence supporting their safety and efficacy. Co-prescribing opioids with other dependence-forming medications (DFMs) causes fatal side effects. Clinicians are advised to avoid combinations of DFMs and, where suitable, deprescribe to improve patient safety., Aim: To review the number of patients registered to the Grange Medical Centre (Nuneaton, Warwickshire) who are co-prescribed an opioid and either benzodiazepine/gabapentinoid for CNCP and to reduce usage of these DFMs., Method: The 'Model for Improvement' is used as a QIP framework. A database search was conducted on 5 October 2023 to identify the cohort of interest. The introduced changes included devising a resource pack outlining the up-to-date non-pharmacological pain management, support channels, and a medication review invitation sent to the identified patients. A pain management template has also been developed to be used by GPs and clinical pharmacists to support the medication review. Guided by the Plan-Do-Study-Act cycle, data will be re-measured to detect incremental changes in practice., Results: In total, 123 patients were receiving co-prescriptions of opioids along with either benzodiazepine/gabapentinoid for CNCP out of the enlisted 12 360 patients. The majority were in the 70-79 years age range. It was also noted that around 66% of patients were females. The QIP's first cycle is currently being implemented., Conclusion: This QIP addresses a pressing need to reduce the usage of DFMs. The interim results will guide the change model in the Grange Medical Centre GP surgery and inform scoping of relevant clinical questions to improve patient safety., (© British Journal of General Practice 2024.)

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.

Objectives: The increase in gabapentinoid prescribing is paralleling the increase in serious harms. To describe the low back pain workers compensation population whose management included a gabapentinoid between 2010 and 2017, and determine secular trends in, and factors associated with gabapentinoid use., Methods: We analysed claim-level and service-level data from the Victorian workers' compensation programme between 1 January 2010 and 31 December 2017 for workers with an accepted claim for a low back pain injury and who had programme-funded gabapentinoid dispensing. Secular trends were calculated as a proportion of gabapentinoid dispensings per year. Poisson, negative binomial and Cox hazards models were used to examine changes over time in incidence and time to first dispensing., Results: Of the 17 689 low back pain claimants, one in seven (14.7%) were dispensed at least one gabapentinoid during the first 2 years (n=2608). The proportion of workers who were dispensed a gabapentinoid significantly increased over time (7.9% in 2010 to 18.7% in 2017), despite a reduction in the number of claimants dispensed pain-related medicines. Gabapentinoid dispensing was significantly associated with an opioid analgesic or anti-depressant dispensing claim, but not claimant-level characteristics. The time to first gabapentinoid dispensing significantly decreased over time from 311.9 days (SD 200.7) in 2010 to 148.2 days (SD 183.1) in 2017., Conclusions: The proportion of claimants dispensed a gabapentinoid more than doubled in the period 2010-2017; and the time to first dispensing halved during this period., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Abstract: Neuropathic corneal pain (NCP) is a new and ill-defined disease characterized by pain, discomfort, aching, burning sensation, irritation, dryness, and grittiness. However, the mechanism underlying NCP remain unclear. Here, we reported a novel rat model of primary NCP induced by long ciliary nerve (LCN) ligation. After sustained LCN ligation, the rats developed increased corneal mechanical and chemical sensitivity, spontaneous blinking, and photophobia, which were ameliorated by intraperitoneal injection of morphine or gabapentin. However, neither tear reduction nor corneal injury was observed in LCN-ligated rats. Furthermore, after LCN ligation, the rats displayed a significant reduction in corneal nerve density, as well as increased tortuosity and beading nerve ending. Long ciliary nerve ligation also notably elevated corneal responsiveness under resting or menthol-stimulated conditions. At a cellular level, we observed that LCN ligation increased calcitonin gene-related peptide (neuropeptide)-positive cells in the trigeminal ganglion (TG). At a molecular level, upregulated mRNA levels of ion channels Piezo2, TRPM8, and TRPV1, as well as inflammatory factors TNF-α, IL-1β, and IL-6, were also detected in the TG after LCN ligation. Meanwhile, consecutive oral gabapentin attenuated LCN ligation-induced corneal hyperalgesia and increased levels of ion channels and inflammation factors in TG. This study provides a reliable primary NCP model induced by LCN ligation in rats using a simple, minimally invasive surgery technique, which may help shed light on the underlying cellular and molecular bases of NCP and aid in developing a new treatment for the disease., (Copyright © 2024 International Association for the Study of Pain.)

Objectives: To evaluate the efficacy of post-operative gabapentin administration as an analgesic agent and its effect on narcotic use after orthopedic surgery in an outpatient sports medicine practice by comparing patients prior to and after initiating the routine use of gabapentin as part of a standardized post-operative pain medication regimen. We hypothesized that adding gabapentin to a multimodal post-operative pain regimen would decrease the number of requested pain medication refills and have no detrimental effect on Visual Analogue Scale and Single Assessment Numerical Evaluation scores at these early post-operative visits., Methods: All outpatient surgical patients, <90 years of age, undergoing outpatient orthopedic surgery by the study's senior author were included between 08/05/2021 and 02/22/2022. Patients were allowed 1 narcotic refill post-operatively and only in the first 3 weeks. The primary outcome was difference in percentage of patients who requested a narcotic refill within 3 weeks post-op. Two- and 6-week Visual Analogue Scale and Single Assessment Numerical Evaluation scores, and baseline health and demographic data. T-tests were run on continuous variables, Chi-Square or Fisher's Exact Test were run on dichotomous variables, and Mann-Whitney U test was run on all other categorical variables. Statistical significance was set at P  < .05 for all tests., Results: There was a significant difference in narcotic refills at 3 weeks: 23 pre-gabapentin patients and 9 post-gabapentin patients (22.8% vs 9.0%, respectively: P  = .006). There were no differences between 2- and 6-week Visual Analogue Scale and 2-week Single Assessment Numerical Evaluation scores. There was a significant difference in 6-week SANE between groups: mean difference = 6.4 ( P  = .027) though less than the established MCID., Conclusion: Addition of gabapentin to a post-operative multimodal pain regimen reduced the use of narcotics after orthopedic sports medicine surgeries while also providing equivalent pain control.

Background: The prevalence of neuropathic pain (NP) in burn patients is reported in the literature to be as high as 80% 1 . Given the complexity of NP in burn patients and the wide range of treatments available, a systematic review of the literature is warranted to summarize our current understanding of management and treatment of NP in this population., Methods: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The following databases were queried to identify relevant articles: PubMed, Cochrane, Embase, Scopus, Ovid, and Web of Science. The main outcome measures were incidence and management of NP. Secondary outcomes included risk factors for NP., Results: Included articles presented findings from 11 different countries, capturing outcomes for 4366 patients. Risk factors for neuropathic pain in burn patients were identified, including older age, alcohol and substance abuse, current daily smoking, greater % total body surface area burns (TBSA), and longer hospitalizations. Pharmacologic treatments included gabapentin/pregabalin (n = 7), ascorbic acid (n = 1), and lidocaine (n = 1). Overall, the studies showed varied results regarding the efficacy of pharmacological treatments. While certain studies demonstrated gabapentanoids to be effective in reducing neuropathic symptoms, others found conflicting results. With regards to non-pharmacologic treatments, electroconvulsive therapy (n = 1), electropuncture (n = 1), nerve release/reconstruction (n = 2), and somatosensory feedback rehabilitation (n = 1) were used and demonstrated promise in reducing pain intensity and improving functionality., Conclusions: Despite NP afflicting the majority of burn patients long after their injury, this systematic review demonstrates insufficient evidence on the pathophysiology, outcomes, and risk factors in NP, as well as the efficacy of various therapies. Future prospective and randomized studies evaluating the etiology of these factors can substantially improve our treatment strategies. This can allow for the development of well-delineated and evidence-based protocols in NP management in hopes of improving quality of life and both psychological and physical function in burn patients., (Copyright © 2024 Elsevier Ltd and ISBI. All rights reserved.)

Background: Disparities in opioid prescribing by race/ethnicity have been described in many healthcare settings, with White patients being more likely to receive an opioid prescription than other races studied. As surgeons increase prescribing of nonopioid medications in response to the opioid epidemic, it is unknown whether postoperative prescribing disparities also exist for these medications, specifically gabapentinoids., Methods: We conducted a retrospective cohort study using a 20% Medicare sample for 2013-2018. We included patients ≥66 years without prior gabapentinoid use who underwent one of 14 common surgical procedures. The primary outcome was the proportion of patients prescribed gabapentinoids at discharge among racial and ethnic groups. Secondary outcomes were days' supply of gabapentinoids, opioid prescribing at discharge, and oral morphine equivalent (OME) of opioid prescriptions. Trends over time were constructed by analyzing proportion of postoperative prescribing of gabapentinoids and opioids for each year. For trends by year by racial/ethnic groups, we ran a multivariable logistic regression with an interaction term of procedure year and racial/ethnic group., Results: Of the 494,922 patients in the cohort (54% female, 86% White, 5% Black, 5% Hispanic, mean age 73.7 years), 3.7% received a new gabapentinoid prescription. Gabapentinoid prescribing increased over time for all groups and did not differ significantly among groups (P = 0.13). Opioid prescribing also increased, with higher proportion of prescribing to White patients than to Black and Hispanic patients in every year except 2014., Conclusions: We found no significant prescribing variation of gabapentinoids in the postoperative period between racial/ethnic groups. Importantly, we found that despite national attention to disparities in opioid prescribing, variation continues to persist in postoperative opioid prescribing, with a higher proportion of White patients being prescribed opioids, a difference that persisted over time., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Prescribing cascades are important contributors to polypharmacy. Little is known about which older adults are at highest risk of experiencing prescribing cascades. We explored which older veterans are at highest risk of the gabapentinoid (including gabapentin and pregabalin)-loop diuretic (LD) cascade, given the dramatic increase in gabapentinoid prescribing in recent years., Methods: Using Veterans Affairs and Medicare claims data (2010-2019), we performed a prescription sequence symmetry analysis (PSSA) to assess loop diuretic initiation before and after gabapentinoid initiation among older veterans (≥66 years). To identify the cascade, we calculated the adjusted sequence ratio (aSR), which assesses the temporality of LD relative to gabapentinoid initiation. To explore high-risk groups, we used multivariable logistic regression with prescribing order modeled as a binary dependent variable. We calculated adjusted odds ratios (aORs), measuring the extent to which factors are associated with one prescribing order versus another., Results: Of 151,442 veterans who initiated a gabapentinoid, there were 1,981 patients who initiated a LD within 6 months after initiating a gabapentinoid compared to 1,599 patients who initiated a LD within 6 months before initiating a gabapentinoid. In the gabapentinoid-LD group, the mean age was 73 years, 98% were male, 13% were Black, 5% were Hispanic, and 80% were White. Patients in each group were similar across patient and health utilization factors (standardized mean difference <0.10 for all comparisons). The aSR was 1.23 (95% CI: 1.13, 1.34), strongly suggesting the cascade's presence. People age ≥85 years were less likely to have the cascade (compared to 66-74 years; aOR 0.74, 95% CI: 0.56-0.96), and people taking ≥10 medications were more likely to have the cascade (compared to 0-4 drugs; aOR 1.39, 95% CI: 1.07-1.82)., Conclusions: Among older adults, those who are younger and taking many medications may be at higher risk of the gabapentinoid-LD cascade, contributing to worsening polypharmacy and potential drug-related harms. We did not identify strong predictors of this cascade, suggesting that prescribing cascade prevention efforts should be widespread rather than focused on specific subgroups., (© 2024 The American Geriatrics Society.)

Purpose: To estimate the combined effect of gabapentinoid and opioid therapy compared to opioid monotherapy on the risk of developing opioid-induced respiratory depression among breast cancer survivors with neuropathic pain., Method: A nested case-control study of Medicare female breast cancer survivors with neuropathic pain receiving both opioids and gabapentinoids, opioid monotherapy, gabapentinoid monotherapy, and none of these drugs was conducted using SEER-Medicare between 2007 and 2015. Cases were survivors with respiratory depression and were matched with controls on the event date (± 1 year), age at diagnosis (± 5 years), and stage at diagnosis. Exposure to opioids and gabapentinoids was assessed 120 days before the event date. Conditional logistic regression was used to assess the impact of exposure among cases and controls., Results: A total of 657 cases and 11,471 controls were identified. After matching, 656 cases and 5612 controls were retained, and cases were more likely to be diagnosed with mental health disorders (24.4% vs 10.5%, p < 0.0001) than controls. In the primary adjusted analysis, combined opioids and gabapentin use were associated with an increased risk of respiratory depression compared to opioid monotherapy (Adj. OR: 1.513; 95% CI: 1.473-2.350). Additionally, under secondary analysis, combined opioids and gabapentin use were associated with an increased risk of respiratory depression compared to receiving neither of these classes. (Adj. OR: 1.595; 95% CI: 1.050-2.421)., Conclusion: There is a need for dose titration strategies of gabapentinoids and caution when co-prescribing opioids and gabapentinoids in older cancer survivors., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)