Characterizing Opioid Prescribing Trends of Medical Oncologists From 2013 to 2019: Analysis From the Centers for Medicare & Medicaid Services Medicare Part D Prescribers Database.

PURPOSE: Opioid prescribing trends in medical oncology are poorly defined past 2017, the year after the CDC updated opioid prescription guidelines in noncancer settings. We aim to characterize pain management by medical oncologists by analyzing opioid and gabapentin prescribing trends from 2013 to 2019, identify physician-related factors associated with prescribing patterns, and assess whether CDC guidelines for nononcologic settings changed prescribing patterns. METHODS: The Centers for Medicare & Medicaid Services (CMS) Medicare Part D Prescribers-by Provider, CMS Medicare Part D Prescribers-by Provider and Drug, and CMS Medicare Physician National Downloadable files from 2013 to 2019 were merged by National Provider Identification. The database included physicians' sex, years of practice, regions, and practice settings. Multivariable binary logistic regression identified significant predictors of total opioid, long-acting opioid, and gabapentin prescriptions. RESULTS: Binary logistic regression modeling revealed no significant difference in mean daily total opioid prescriptions from 2013 to 2017. Daily opioid prescriptions by medical oncologists decreased significantly after 2017 (P < .001). Increased opioid prescribing was associated with physician male sex (P < .001), practicing over 10 years (P < .001), and practice in nonurban areas (P < .001). Opioid prescribing was greatest in the South and Midwest United States (P < .001). The same patterns were observed with total long-acting opioid prescriptions, whereas gabapentin prescribing increased from 2013 to 2019 (P < .001). CONCLUSION: Opioid prescriptions by medical oncologists decreased significantly from 2013 to 2019, but this decrease was most substantial from 2017 to 2019. These results may imply that the 2016 CDC guidelines influenced medical oncologists, particularly more junior physicians in urban settings, to manage chronic cancer pain with alternative therapies.

Non-oestrogen-based and complementary therapies for menopause.

Women are living a significant portion of their adult lives in the post-reproductive phase, and many seek help for debilitating menopausal symptoms. Every individual's experience of menopausal transition is unique. Adopting a holistic approach to managing the menopause using a combination of lifestyle, hormonal, and non-hormonal interventions is key to maximise the quality of life of affected women. However, many opt to use non hormonal options or have contraindications to using hormonal therapy. Studies have shown that several pharmacological non-hormonal medications such as SSRIs, SSRI/SNRIs, Gabapentin, and Pregabalin are effective for managing vasomotor symptoms as well as other menopausal symptoms. Their main side effects are dry mouth, nausea, constipation, reduced libido, and loss of appetite. Clonidine is the only non-hormonal drug which is licenced for control of vasomotor symptoms in the UK, but has several side effects including dizziness and sleep disturbance. Cognitive Behavioural Therapy is recommended as a treatment for anxiety, sleep problems and vasomotor symptoms related to menopausal transition. Evidence for clinical efficacy and safety of herbal remedies and alternative therapies remains weak. Studies with neurokinin receptor 3 antagonists on women with hot flushes have shown improvement in vasomotor symptoms and results of large-scale studies are awaited.

Association between chiropractic spinal manipulation and gabapentin prescription in adults with radicular low back pain: retrospective cohort study using US data.

OBJECTIVES: Radicular low back pain (rLBP) is often treated off-label with gabapentin or by chiropractors using chiropractic spinal manipulative therapy (CSMT). To date, no studies have examined the association between these interventions. We hypothesised that adults under 50 years of age receiving CSMT for newly diagnosed rLBP would have reduced odds of receiving a gabapentin prescription over 1 year-follow-up. DESIGN: Retrospective cohort study. SETTING: US network including linked medical records, medical claims and pharmacy claims of >122 million patients attending large healthcare organisations (TriNetX), queried 15 June 2023, yielding data from 2017 to 2023. PARTICIPANTS: Adults aged 18-49 were included at their first occurrence of rLBP diagnosis. Exclusions were severe pathology, other spinal conditions, on-label gabapentin indications and gabapentin contraindications. Propensity score matching controlled for variables associated with gabapentin use and receipt of prescription medication over the preceding year. INTERVENTIONS: Patients were divided into CSMT or usual medical care cohorts based on the care received on the index date of rLBP diagnosis. PRIMARY AND SECONDARY OUTCOME MEASURES: OR for gabapentin prescription. RESULTS: After propensity matching, there were 1635 patients per cohort (mean age 36.3±8.6 years, 60% women). Gabapentin prescription over 1-year follow-up was significantly lower in the CSMT cohort compared with the usual medical care cohort, with an OR (95% CI) of 0.53 (0.40 to 0.71; p<0.0001). Sensitivity analyses revealed early divergence in cumulative incidence of prescription; and no significant between-cohort difference in a negative control outcome (gastrointestinal medication) suggesting adequate control for pharmacological care preference. CONCLUSIONS: Our findings suggest that US adults receiving CSMT for newly diagnosed rLBP have significantly reduced odds of receiving a gabapentin prescription over 1-year follow-up compared with those receiving usual medical care. Results may not be generalisable and should be replicated in other healthcare settings and corroborated by a prospective study to reduce confounding.

Therapeutic Strategies for Postherpetic Neuralgia: Mechanisms, Treatments, and Perspectives.

PURPOSE OF REVIEW: Postherpetic neuralgia is an annoying pain that mainly affects older people. In order to give patients more options, this review summarizes the pharmacological and interventional treatments for postherpetic neuralgia and updates the research on the efficacy, thereby providing doctors with more treatment options. The adverse effects and effective doses of its various treatments are also presented so that the therapy can be prescribed according to their concrete physical conditions. In a word, this review is dedicated to providing a comprehensive overview of the treatment options for postherpetic neuralgia and offering patients more choices. RECENT FINDINGS: Combinational therapy is more excellent than monotherapy. The local anesthesia and gabapentin comprised outstanding compatibility. In addition, two therapeutic tools for PHN patients, especially for the intractable ones, electroacupuncture (EA), and osteopathic manipulative treatment (OMT), show their efficacy and become potential options to alleviate pain. In terms of treatment, guidelines recommend patients use tricyclic antidepressants (TCAs), gabapentin, pregabalin, and 5% lidocaine patches as the first-line medications, and gabapentin is investigated most, especially the gabapentin enacarbil (GEn). And drug efficacy can be limited by adverse effects and tolerated doses. Interventional treatments, with their invasiveness and operational difficulty, are usually considered for intractable patients. Combinational therapies may be used when a single therapy cannot achieve the desired effect. Therapies such as OMT and EA have also been proposed to palliate pain in some cases, and future directions of treatment may be investigated in Chinese medicine and acupuncture.

Prevalence of opioid and nonopioid pain management therapies among Medicare beneficiaries with musculoskeletal pain conditions from 2016 to 2019.

INTRODUCTION: Pain treatment guidelines prioritize nonopioid therapies over opioid medications to prevent opioid-related harms. We examined trends in receipt and intensity of nonpharmacologic, nonopioid medication, and opioid therapies among Medicare beneficiaries. METHODS: Using a 20% national random sample of Medicare data from 2016 to 2019, we identified fee-for-service beneficiaries with ≥2 diagnoses of back, neck, fibromyalgia, or osteoarthritis/joint pain annually. We excluded beneficiaries with cancer. We calculated annual proportions of beneficiaries who received physical therapy (PT), chiropractic care, gabapentin, and opioids, overall and in demographic, geographic, and clinical subgroups. We estimated the intensity of therapies using the annual number of visitsor prescription fills, prescription days' supply, and opioid dose. RESULTS: During 2016-2019, PT receipt increased (22.8% to 25.5%) and the mean number of visits among recipients of PT went from 12 to 13. Chiropractic receipt (~18%) and mean annual visits (~10) remained unchanged. The prevalence of gabapentin receipt was stable at ~22% and the mean annual number of fills was unchanged though gabapentin days increased slightly. Opioid prescribing decreased (56.7% to 46.5%) and reductions in opioid dose and duration were observed. Opioid receipt was high among beneficiaries who were under 65 years, American Indian/Alaska Native, Black/African American, or had opioid use disorder (OUD), in whom nonpharmacologic therapies were also received the least. CONCLUSION: Utilization of nonopioid therapies lagged opioids among Medicare beneficiaries with musculoskeletal pain, with limited changes from 2016 to 2019. As opioid prescribing declines and alternative pain therapy receipt remains low, there are potential increasing risks of pain going untreated or undertreated and individuals seeking illicit opioids to alleviate their pain.

Efficacy and Safety of Gabapentin in Improving Sleep Quality of Patients with Sensory Nervous System Diseases: A Meta-Analysis.

Context: Sensory nervous-system diseases are chronic diseases that injury or disease of the somatosensory nervous system causes. Sleep disorders usually accompany these diseases, and in turn, worsen their conditions and form a vicious circle that brings great difficulties in clinical treatment. Objective: The study intended to systematically evaluate the clinical efficacy and safety of gabapentin in improving the sleep quality of patients with sensory nervous-system diseases using a meta-analysis, so as to provide evidence-based medical evidence for clinical treatment. Design: The research team performed a comprehensive narrative review by searching the China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal (VIP), WANFANG, Chinese Biomedical Database (CBM), PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases. The search terms included gabapentin, 1-(aminomethyl)-cyclohexaneacetic acid, gabapentin hexal, gabapentin-ratiopharm, sleep, and insomnia. Setting: The review took place in the Department of Neurology at the First People's Hospital of Linping District in Hangzhou, China. Outcome Measures: The research team extracted the data from the studies meeting the inclusion criteria and then transferred them into the Review Manager 5.3 software for meta-analysis. The outcome measures included scores: (1) for the improvement in the degree of sleep interference score; (2) for the improvement in sleep quality; (3) for the rate of poor sleep quality; (4) for the rate awakenings of >5 per night; and (5) for the incidence of adverse reactions. Results: The research team found eight RCTs with 1269 participants, including 637 participants in a gabapentin test group and 632 participants in the placebo control group. The meta-analysis showed that the decrease in the degree of sleep interference [mean deviation (MD) = -0.86, 95% CI: (-0.91, -0.82), P < .00001] and the improvement in sleep quality [odds ratio (OR) = 2.64, 95% CI: (1.90, 3.67), P < .00001] in gabapentin group were significantly higher than those in placebo group (P < .05), while the rate of poor sleep quality [OR = 0.43, 95% CI: (0.23, 0.79), P = .007] and the rate of > 5 night awakenings [OR = 0.01, 95% CI: (0.05, 0.70), P = .01] in gabapentin group were significantly lower than those in placebo group (P < .05). No statistically significant differences existed in the incidence of adverse reactions between the two groups. Conclusions: Gabapentin is safe and effective in improving the sleep quality of patients with sensory nervous-system diseases. Due to the limitations of sample size and types of diseases in the current study, the field needs multicenter, large-sample, and high-quality RCTs for further validation in the future.

Comparison the effect of valerian and gabapentin on RLS and sleep quality in hemodialysis patients: A randomized clinical trial.

INTRODUCTION: This study aimed to compare the effect of valerian and gabapentin on restless legs syndrome (RLS) and sleep quality in HD patients. METHODS: In this cross over clinical trial study, 40 HD patients allocated into a valerian and gabapentin group. In the first phase of the study, Group A received valerian and Group B received gabapentin 1 h before bedtime for 1 month. In the second phase, the two groups' treatment regimen was swapped. After a 1-month washout period, the same process was repeated on the crossover groups. RESULTS: After the first phase, the mean score of RLS was lower in the gabapentin group. But there was no statistically significant difference between the two groups in terms of sleep quality score before and after the first and second interventions. CONCLUSION: Gabapentin is more effective than valerian in improving RLS, but both are equally effective in improving sleep quality.

Comparative Efficacy of Adjuvant Nonopioid Analgesia in Adult Cardiac Surgical Patients: A Network Meta-Analysis.

OBJECTIVES: To compare the relative efficacy of adjuvant nonopioid analgesic regimens in adult cardiac surgical patients. DESIGN: This frequentist, random-effects network meta-analysis (NMA) was prospectively registered on PROSPERO (CRD42021282913) and conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses for Network Meta-Analyses (PRISMA-NMA). The risk of bias (RoB) and confidence of evidence were assessed by RoB 2 and Confidence in Network Meta-Analysis, respectively. Relevant databases were searched from inception to October 9, 2021. SETTING: A total of 124 (N = 26,257) randomized controlled trials were included, of which 110 were analyzed. PARTICIPANTS: Trials enrolling adults (≥18 years of age) undergoing cardiac surgery that compared nonopioid analgesics against other nonopioid analgesics, placebo, or no additional treatment, as adjuvants to standard analgesic management, and reported at least 1 of the outcomes of interest. MEASUREMENT AND MAIN RESULTS: Outcomes of interest included resting postoperative pain scores at 24 hours. Compared with standard care and/or placebo, pain scores were reduced significantly by 10 different regimens, including acetaminophen (N = 176; mean difference [MD] -0.66 points, 95% CI -1.16 to -0.15 points; high confidence), magnesium (N = 323; -0.05 points, 95% CI -0.07 to -0.02 points; high confidence), gabapentin (N = 96; MD -0.40 points, 95% CI -0.71 to -0.09; moderate confidence), and clonidine (N = 64; MD v0.38 points, 95% CI -0.73 to v0.04 points; moderate confidence). Indomethacin, diclofenac, magnesium, and gabapentin significantly reduced 24-hour opioid consumption. Four regimens significantly decreased the intensive care unit length of stay. Hydrocortisone, dexmedetomidine, and clonidine significantly decreased the duration of mechanical ventilation. Magnesium decreased, while methylprednisolone significantly increased, the risk of myocardial infarction. CONCLUSIONS: Given the increasing emphasis on enhanced recovery after surgery(ERAS) protocols and the eventual goal of limiting opiate prescriptions postoperatively, the authors' data suggested far greater use of nonopioid adjuncts to minimize pain and enhance recovery following cardiac surgery.

Case Series: Synergistic Effect of Gabapentin and Adjuvant Pregabalin in Neuropathic Pain.

Gabapentin and pregabalin both exert high affinity to the α2δ subunit of the voltage-gated calcium channels which inhibits excitatory neurotransmitter release. The synergistic mechanism was described in rats given combinations of gabapentin and pregabalin. In this case series, we described 2 cases which may illustrate the synergistic effect of gabapentin and pregabalin in treatment resistant neuropathic pain. Low dose pregabalin was added to therapeutic gabapentin to achieve appreciable pain reduction in one case and improved quality of life in another case. Further research with more enrollment and longer study duration may help elucidate the appropriate dosing and potential associated side effects.

Exploration of restless legs syndrome under the new concept: A review.

Restless leg syndrome (Restless legs syndrome, RLS) is a common neurological disorder. The pathogenesis of RLS remains unknown, and recent pathophysiological developments have shown the contribution of various genetic markers, neurotransmitter dysfunction, and iron deficiency to the disease, as well as other unidentified contributing mechanisms, particularly chronic renal dysfunction. RLS enhancement syndrome is frequently observed in patients with RLS who have received long-term dopamine agonist therapy, manifesting as a worsening of RLS symptoms, usually associated with an increase in the dose of dopamine agonist. Some patients with RLS can adequately control their symptoms with non-pharmacological measures such as massage and warm baths. First-line treatment options include iron supplementation for those with evidence of reduced iron stores, or gabapentin or pregabalin, as well as dopamine agonists, such as pramipexole. Second-line therapies include opioids such as tramadol. RLS seriously affects the quality of life of patients, and because its pathogenesis is unclear, more biological evidence and treatment methods need to be explored.

Treatment modalities in brachioradial pruritis: a systematic review.

INTRODUCTION: Brachioradial pruritis is a rare dysesthesia syndrome that is known to negatively impact quality of life. No consensus exists regarding optimal treatment strategies. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Collaboration Clinical Trials Registry from 1966 to 2021 for studies using the title word "brachioradial pruritis" with no language restriction. One author (A.Z.) screened and performed full article reviews of all randomized clinical trials, cohort studies, case-control studies, case reports, and case series describing treatment outcomes among patients with brachioradial pruritis. RESULTS: We identified 239 potential articles with a final set of 45 articles meeting inclusion criteria. Only a single randomized clinical trial was identified, finding no significant benefit of topical capsaicin cream. Treatment modalities with the greatest number of reported successful therapeutic trials include gabapentin and tricyclic antidepressants. In patients with confirmed cervical spine disease, spine-directed therapies such as epidural injections were found to be beneficial. Case reports and small case series describing less-common treatments were also identified. DISCUSSION: The literature is overall limited with the greatest support for gabapentin, pregabalin, tricyclic antidepressants, and spine-directed therapies in appropriate patients with brachioradial pruritis. Future randomized clinical trials are needed to compare the relative effectiveness of available treatments.

Efficacy and safety of different antidepressants and anticonvulsants in central poststroke pain: A network meta-analysis and systematic review.

OBJECTIVE: To evaluate the efficacy and safety of different antidepressants and anticonvulsants in the treatment of central poststroke pain (CPSP) by network meta-analysis and provide an evidence-based foundation for clinical practice. METHODS: PubMed, Cochrane Library, EMBASE, CNKI, APA PsycINFO, Wanfang, VIP and other databases were searched by computer to find clinical randomized controlled studies (RCTs) on drug treatment of CPSP. The retrieval time limit was from the establishment of each database to July 2022. The quality of the included RCTs was evaluated using the bias risk assessment tool recommended by Cochrane. Stata 14.0 was used for network meta-analysis. RESULTS: A total of 13 RCTs, 1040 patients and 9 drugs were finally included. The results of the network meta-analysis showed that the effectiveness ranking as rated by the visual analog scale (VAS) was gabapentin > pregabalin > fluoxetine > lamotrigine > duloxetine > serqulin > amitriptyline > carbamazepine > vitamin B. Ranking according to the numerical rating scale (NRS) was pregabalin > gabapentin > carbamazepine. Ranking derived from the Hamilton depression scale (HAMD) was pregabalin > duloxetine > gabapentin > amitriptyline. CONCLUSION: All nine drugs can relieve the pain of CPSP patients to different degrees; among them pregabalin and gabapentin have the most significant effect, and gabapentin and pregabalin also have the most adverse reactions. In the future, more multicenter, large sample, double-blind clinical randomized controlled trials need to be carried out to supplement and demonstrate the results of this study.

The interplay of epilepsy with impaired mitophagy and autophagy linked dementia (MAD): A review of therapeutic approaches.

The duration and, age of dementia have been linked to a higher risk of seizures. The exact mechanism that drives epileptogenesis in impaired mitophagy and autophagy linked dementia (MAD) is fully defined after reviewing the Scopus, Publon, and Pubmed databases. The epileptogenesis in patients with Alzheimer's disease dementia (ADD) and Parkinson's disease dementia (PDD) is due to involvement of amyloid plaques (Aß), phosphorylated tau (pTau), Parkin, NF-kB and NLRP3 inflammasome. Microglia, the prime protective and inflammatory cells in the brain exert crosstalk between mitophagy and inflammation. Several researchers believed that the inflammatory brain cells microglia could be a therapeutic target for the treatment of a MAD associated epilepsy. There are conventional antiepileptic drugs such as gabapentin, lamotrigine, phenytoin sodium, carbamazepine, oxcarbazepine, felbamate, lamotrigine, valproate sodium, and topiramate are prescribed by a psychiatrist to suppress seizure frequency. Also, the conventional drugs generate serious adverse effects and synergises dementia characteristics. The adverse effect of carbamazepine is neurotoxic and also, damages haemopoietic system and respiratory tract. The phenytoin treatment causes cerebellar defect and anemia. Dementia and epilepsy have a complicated relationship, thus targeting mitophagy for cure of epileptic dementia makes sense. Complementary and alternative medicine (CAM) is one of the rising strategies by many patients of the world, not only to suppress seizure frequency but also to mitigate dementia characteristics of patients. Therefore our present review focus on the interplay between epilepsy and MAD and their treatment with CAM approaches.

Treating Severe Refractory and Augmented Restless Legs Syndrome.

Restless legs syndrome (RLS) is a sensory-motor neurologic disorder present to a clinically significant degree in 2% to 3% of the adult population, more commonly with advancing age and in women, that dramatically affects sleep and quality of life. Addressing factors that worsen RLS (eg, iron deficiency, antidepressant or antihistamine administration, OSA) is an important first step in treatment. RLS can generally be well treated with medications such as the alpha2-delta calcium channel ligands (A2Ds) gabapentin, pregabalin, and gabapentin enacarbil or, if these are poorly tolerated or lack efficacy, the dopamine agonists (DAs) pramipexole, ropinirole, or rotigotine. Oral or IV iron supplementation is often efficacious as initial treatment in patients with low normal serum indexes. However, at least one-third of patients do not achieve acceptable symptom relief from initial treatments. Furthermore, DAs, the most commonly used medications for RLS, commonly produce augmentation, a progressive, long-term, iatrogenic worsening of RLS symptoms characterized by increasing severity as well as temporal and anatomic extension of symptoms. If dopaminergic augmentation of RLS is present, substitution of an A2D or opioid for the DA is the primary goal. However, given the profound rebound RLS and insomnia that occurs with even small dose reductions of DAs, the initial change should be the addition of one of these alternate treatments. Once adequate doses, or symptom relief, are achieved with the second agent, subsequent very slow down-titration and discontinuation of the DA is often possible and can lead to dramatic long-term relief of RLS symptoms and improvement in sleep.

Results from a randomized, double-blind, placebo-controlled, crossover, multimodal-MRI pilot study of gabapentin for co-occurring bipolar and cannabis use disorders.

Disrupted brain gamma-aminobutyric acid (GABA)/glutamate homeostasis is a promising target for pharmacological intervention in co-occurring bipolar disorder (BD) and cannabis use disorder (CUD). Gabapentin is a safe and well-tolerated medication, FDA-approved to treat other neurological diseases, that restores GABA/glutamate homeostasis, with treatment studies supporting efficacy in treating CUD, as well as anxiety and sleep disorders that are common to both BD and CUD. The present manuscript represents the primary report of a randomized, double-blind, placebo-controlled, crossover (1-week/condition), multimodal-MRI (proton-MR spectroscopy, functional MRI) pilot study of gabapentin (1200 mg/day) in BD + CUD (n = 22). Primary analyses revealed that (1) gabapentin was well tolerated and adherence and retention were high, (2) gabapentin increased dorsal anterior cingulate cortex (dACC) and right basal ganglia (rBG) glutamate levels and (3) gabapentin increased activation to visual cannabis cues in the posterior midcingulate cortex (pMCC, a region involved in response inhibition to rewarding stimuli). Exploratory evaluation of clinical outcomes further found that in participants taking gabapentin versus placebo, (1) elevations of dACC GABA levels were associated with lower manic/mixed and depressive symptoms and (2) elevations of rBG glutamate levels and pMCC activation to cannabis cues were associated with lower cannabis use. Though promising, the findings from this study should be interpreted with caution due to observed randomization order effects on dACC glutamate levels and identification of statistical moderators that differed by randomization order (i.e. cigarette-smoking status on rBG glutamate levels and pMCC cue activation). Nonetheless, they provide the necessary foundation for a more robustly designed (urn-randomized, parallel-group) future study of adjuvant gabapentin for BD + CUD.

Punicalagin and ellagic acid containing Punica granatum L. fruit rind extract prevents vincristine-induced neuropathic pain in rats: an in silico and in vivo evidence of GABAergic action and cytokine inhibition.

Objectives: We aimed to investigate the protective potential of Punica granatum L. fruit rind extract (PFE) containing punicalagin (10.3% W/W), ellagic acid (EA) (2.7%W/W) in vincristine (75 µg/kg i.p.)- induced neuropathic pain in Wistar rats.Methods: Docking simulation studies were done on the three-dimensional (3D) structure of the GABAA and PPAR γ receptor for the binding of EA as well as punicalagin docking studies on TNF-α, and IL-6. The Present Study conceptualized a test battery to evaluate the behavioral, biochemical and histological changes.Results: Vincristine -induced significant cold allodynia, mechanical hyperalgesia, and functional deficit on 12th and 21st days. It also increased in the levels of TNF-α (Tumor necrosis factor-α), IL-6 (Interleukin-6), and MPO (Myeloperoxidase). Administration of PFE (100 and 300 mg/kg, p.o.), EA (50 mg/kg), and gabapentin (100 mg/kg) attenuated Vincristine-induced behavioral and biochemical changes significantly (P < .05). PFE showed better antinociceptive activity to EA. The histopathological evaluation also revealed the protective effects of PFE. Pretreatment of bicuculline (selective antagonist of GABAA receptors) reversed antinociceptive action of PFE, but administration of γ aminobutyric acid potentiated the action of PFE. PPAR-γ antagonist BADGE did not modify the effect of PFE. Docking results revealed that EA properly positioned into GABA and PPARγ binding site and acts as a partial agonist. Docking score of Punicalagin found to be - 9.02 kcal/mol and - 8.32 kcal/mol on IL-6 and TNFα respectively.Discussion: Conclusively, the attenuating effect of PFE may be attributed to the GABAergic system, cytokine inhibition, and anti-inflammatory activities.

Mechanisms, Characteristics, and Treatment of Neuropathic Pain and Peripheral Neuropathy Associated with Dinutuximab in Neuroblastoma Patients.

Prognosis of metastatic neuroblastoma is very poor. Its treatment includes induction chemotherapy, surgery, high-dose chemotherapy, radiotherapy, and maintenance with retinoic acid, associated with the anti-GD2 monoclonal antibody (ch14.18) dinutuximab. Immunotherapy determined a significant improvement in survival rate and is also utilized in relapsed and resistant neuroblastoma patients. Five courses of dinutuximab 100 mg/m2 are usually administered as a 10-day continuous infusion or over 5 consecutive days every 5 weeks. Dinutuximab targets the disialoganglioside GD2, which is highly expressed on neuroblastoma cells and minimally present on the surface of normal human neurons, peripheral pain fibers, and skin melanocytes. Anti GD2 antibodies bind to surface GD2 and determine the lysis of neuroblastoma cells induced by immune response via the antibody-dependent cellular cytotoxicity and the complement-dependent cytotoxicity. Dinutuximab has significant side effects, including neuropathic pain, peripheral neuropathy, hypersensitivity reactions, capillary leak syndrome, photophobia, and hypotension. The most important side effect is neuropathic pain, which is triggered by the same antibody-antigen immune response, but generates ectopic activity in axons, which results in hyperalgesia and spontaneous pain. Pain can be severe especially in the first courses of dinutuximab infusion, and requires the administration of gabapentin and continuous morphine infusion. This paper will focus on the incidence, mechanisms, characteristics, and treatment of neuropathic pain and peripheral neuropathy due to dinutuximab administration in neuroblastoma patients.

Thermographic follow-up of postherpetic neuralgia (PHN) subsequent to Ramsay Hunt syndrome with multicranial nerve (V, VII, VIII and IX) involvement: a case report.

BACKGROUND: Ramsay Hunt syndrome (RHS) is caused by a reactivation of varicella-zoster virus (VZV) infection, and it is characterized by the symptoms of facial paralysis, otalgia, auricular rash, and/or an oral lesion. Elderly patients or immunocompromised patients, deep pain at the initial visit and no prompt treatment are significant predictors of postherpetic neuralgia (PHN). When PHN occurs, especially involved cranial polyneuropathy, multiple modalities should be administered for patients with the intractable PHN. The use of thermography in the follow-up of PHN secondary to RHS with multicranial nerve involvement has not yet been described yet in the literature. CASE PRESENTATION: The patient was a 78-year-old man with the chief complaint of a 3-month history of PHN secondary to RHS with polycranial nerve (V, VII, VIII, and IX) involvement. Multimodality therapy with oral gabapentin, pulsed radiofrequency (PRF) application to the Gasserian ganglion for pain in the trigeminal nerve region, linear-polarized near-infrared light irradiation for pain in the facial nerve region, and 2% lidocaine spray for pain in the glossopharyngeal nerve region was used to the treat patient, and follow-up evaluations included thermography. This comprehensive treatment obviously improved the quality of life, resulting in considerable pain relief, as indicated by a decrease in the numerical rating scale (NRS) score from 9 to 3 and a decrease in thermal imaging temperature from higher to average temperature on the ipsilateral side compared with the contralateral side. Lidocaine spray on the tonsillar branches of the glossopharyngeal nerve resulted in an improvement in odynophagia, and the NRS score decreased from 9 to 0 for glossopharyngeal neuralgia after three applications. CONCLUSION: Although the use of thermography in the follow-up of RHS with multiple cranial nerve (V, VII, VIII, and IX) involvement is very rare, in this patient, thermal imaging showed the efficacy of combination therapy (oral gabapentin, 2% lidocaine sprayed, PRF application and linear-polarized near-infrared light irradiation) and that is a good option for treatment.

Paracervical blocks facilitate timely brachytherapy amidst COVID-19.

PURPOSE: The COVID-19 pandemic presents serious challenges for brachytherapists, and in the time-sensitive case of locally advanced cervical cancer, the need for curative brachytherapy (BT) is critical for survival. Given the high-volume of locally advanced cervical cancer in our safety-net hospital, we developed a strategy in close collaboration with our gynecology oncology and anesthesia colleagues to allow for completely clinic-based intracavitary brachytherapy (ICBT). METHODS AND MATERIALS: This technical report will highlight our experience with the use of paracervical blocks (PCBs) and oral multimodal analgesia (MMA) for appropriately selected cervical ICBT cases, allowing for completely clinic-based treatment. RESULTS: 18 of 19 (95%) screened patients were eligible for in-clinic ICBT. The excluded patient had significant vaginal fibrosis. 38 of 39 intracavitary implants were successfully transitioned for entirely in-clinic treatment utilizing PCBs and oral MMA (97% success rate). One case was aborted due to inadequate analgesia secondary to a significantly delayed case start time (PO medication effect diminished). 95% of patients reported no pain at the conclusion of the procedure. The median (IQR) D2cc for rectum and bladder were 64.8 (58.6-70.2) Gy and 84.1 (70.9-89.4) Gy, respectively. Median (IQR) CTV high-risk D90 was 88.0 (85.6-89.8) Gy. CONCLUSIONS: In a multidisciplinary effort, we have successfully transitioned many ICBT cases to the clinic with the use of PCB local anesthesia and oral multimodality therapy in direct response to the current pandemic, thereby mitigating exposure risk to patients and staff as well as reducing overall health care burden.

Involvement of Oxidative Stress and Nerve Growth Factor in Behavioral and Biochemical Deficits of Experimentally Induced Musculoskeletal Pain in Mice: Ameliorative Effects of Heraclin.

Musculoskeletal pain is a widespread complex regional pain syndrome associated with altered emotional and cognitive functioning along with heightened physical disability that has become a global health concern. Effective management of this disorder and associated disabilities includes accurate diagnosis of its biomarkers and instituting mechanism-based therapeutic interventions. Herein, we explored the role of heraclin, a plant-derived molecule, in musculoskeletal pain and its underlying mechanistic approaches in an experimental mouse model. Reserpine (0.5 mg/kg) for 3 consecutive days evoked hyperalgesia, motor incoordination, lack of exploratory behavior, anxiety, and cognition lapse in mice. Reserpine-challenged mice displayed higher serum cytokine level, altered brain neurotransmitter content, elevated brain and muscle oxidative stress, and upregulated brain nerve growth factor receptor expression. Treatment with heraclin (10 mg/kg for 5 consecutive days) exerted analgesic effect and improved motor coordination and memory deficits in mice. Heraclin arrested serum cytokine rise, normalized brain neurotransmitter content, reduced tissue oxidative stress, and downregulated the nerve growth factor receptor expression. Therefore, it may be suggested that heraclin exerts beneficial effects against reserpine-induced musculoskeletal pain disorder possibly through the attenuation of NGFR-mediated pain and inflammatory signaling. Graphical Abstract.