Advances and challenges in neuropathic pain: a narrative review and future directions.

Over the past few decades, substantial advances have been made in neuropathic pain clinical research. An updated definition and classification have been agreed. Validated questionnaires have improved the detection and assessment of acute and chronic neuropathic pain; and newer neuropathic pain syndromes associated with COVID-19 have been described. The management of neuropathic pain has moved from empirical to evidence-based medicine. However, appropriately targeting current medications and the successful clinical development of drugs acting on new targets remain challenging. Innovative approaches to improving therapeutic strategies are required. These mainly encompass rational combination therapy, drug repurposing, non-pharmacological approaches (such as neurostimulation techniques), and personalised therapeutic management. This narrative review reports historical and current perspectives regarding the definitions, classification, assessment, and management of neuropathic pain and explores potential avenues for future research.

Gabapentin initiation in the inpatient setting: A characterization of prescribing.

PURPOSE: Gabapentin is a widely prescribed analgesic with increased popularity over recent years. Previous studies have characterized use of gabapentin in the outpatient setting, but minimal data exist for its initiation in the inpatient setting. The objective of this study was to characterize the prescribing patterns of gabapentin when it was initiated in the inpatient setting. METHODS: This was a retrospective cohort study of a random sample of adult patients who received new-start gabapentin during hospital admission. Patients for whom gabapentin was prescribed as a home medication, with one-time, on-call, or as-needed orders, or who died during hospital admission were excluded. The primary outcome was characterization of the gabapentin indication; secondary outcomes included the starting and discharge doses, the number of dose titrations, the rate of concomitant opioid prescribing, and pain clinic follow-up. Patients were stratified by surgical vs nonsurgical status. RESULTS: A total of 464 patients were included, 283 (61.0%) of whom were surgical and 181 (39.0%) of whom were nonsurgical. The cohort was 60% male with a mean (SD) age of 56 (18) years; surgical patients were younger and included more women. The most common indications for surgical patients were multimodal analgesia (161; 56.9%), postoperative pain (53; 18.7%), and neuropathic pain (26; 9.2%), while those for nonsurgical patients were neuropathic pain (72; 39.8%) and multimodal analgesia (53; 29.3%). The mean starting dose was similar between the subgroups (613 mg for surgical patients vs 560 mg for nonsurgical patients; P = 0.196). A total of 51.6% vs 81.8% of patients received gabapentin at discharge (P < 0.0001), while referral/follow-up to a pain clinic was minimal and similar between the subgroups (1.1% vs 3.9%; P = 0.210). CONCLUSION: Inpatients were commonly initiated on gabapentin for generalized indications, with approximately half discharged on gabapentin. Further studies are needed to assess the impact of this prescribing on chronic utilization.

α-Conotoxin RgIA and oligoarginine R8 in the mice model alleviate long-term oxaliplatin induced neuropathy.

Оligoarginines were recently discovered (Lebedev et al., 2019 Nov) as a novel class of nicotinic acetylcholine receptors (nAChRs) inhibitors, octaoligoarginine R8 showing a relatively high affinity (44 nM) for the α9/α10 nAChR. Since the inhibition of α9/α10 nAChR by α-conotoxin RgIA and its analogs is a possible way to drugs against neuropathic pain, here in a mice model we compared R8 with α-conotoxin RgIA in the effects on the chemotherapy-induced peripheral neuropathy (CIPN), namely on the long-term oxaliplatin induced neuropathy. Tests of cold allodynia, hot plate, Von Frey and grip strength analysis revealed for R8 and α-conotoxin RgIA similar positive effects, expressed most prominently after two weeks of administration. Histological analysis of the dorsal root ganglia sections showed for R8 and RgIA a similar partial correction of changes in the nuclear morphology of neurons. Since α9/α10 nAChR might be not the only drug target for R8, we analyzed the R8 action on rat TRPV1 and TRPA1, well-known nociceptive receptors. Against rTRPV1 at 25 µM there was no inhibition, while for rTRPA1 IC50 was about 20 µM. Thus, involvement of rTRPA1 cannot be excluded, but in view of the R8 much higher affinity for α9/α10 nAChR the latter seems to be the main target and the easily synthesized R8 can be considered as a potential candidate for a drug design.

Neuropathic pain post-COVID-19: a case report.

A 61-year-old man with no significant medical history developed fever, headache and mild shortness of breath. He tested positive for SARS-CoV-2 and self-isolated at home, not requiring hospital admission. One week after testing positive, he developed acute severe burning pain affecting his whole body, subsequently localised distally in the limbs. There was no ataxia or autonomic failure. Neurological examination was unremarkable. Electrophysiological tests were unremarkable. Skin biopsy, lumbar puncture, enhanced MRI of the brachial plexus and MRI of the neuroaxis were normal. His pain was inadequately controlled with pregabalin but improved while on a weaning regimen of steroids. This case highlights the variety of possible symptoms associated with SARS-CoV-2 infection.

Novel Sigma 1 Receptor Antagonists as Potential Therapeutics for Pain Management.

The sigma 1 receptor (S1R) is a molecular chaperone protein located in the endoplasmic reticulum and plasma membranes and has been shown to play important roles in various pathological disorders including pain and, as recently discovered, COVID-19. Employing structure- and QSAR-based drug design strategies, we rationally designed, synthesized, and biologically evaluated a series of novel triazole-based S1R antagonists. Compound 10 exhibited potent binding affinity for S1R, high selectivity over S2R and 87 other human targets, acceptable in vitro metabolic stability, slow clearance in liver microsomes, and excellent blood-brain barrier permeability in rats. Further in vivo studies in rats showed that 10 exhibited negligible acute toxicity in the rotarod test and statistically significant analgesic effects in the formalin test for acute inflammatory pain and paclitaxel-induced neuropathic pain models during cancer chemotherapy. These encouraging results promote further development of our triazole-based S1R antagonists as novel treatments for pain of different etiologies.

Standard headache and neuralgia treatments and SARS-CoV-2: opinion of the Spanish Society of Neurology's Headache Study Group. / Tratamientos habituales utilizados en cefaleas, neuralgias y SARS-CoV-2. Posicionamiento del grupo de estudio de cefaleas de la Sociedad Española de Neurología.

INTRODUCTION: In recent months, doubts have arisen among patients, general practitioners, and neurologists as to whether some drugs commonly used in patients with headaches and neuralgia may favour or complicate the disease caused by SARS-CoV-2. MATERIAL AND METHODS: We collected information on the opinions of scientific societies and medicines agencies (American, European, and Spanish) to clarify doubts regarding the use of drugs such as lisinopril, candesartan, ibuprofen, corticosteroids, carbamazepine, and monoclonal antibodies targeting the calcitonin gene-related peptide in the context of the COVID-19 pandemic. RESULTS: We make recommendations about the use of standard headache treatments in the context of the COVID-19 pandemic, based on the current scientific evidence. CONCLUSIONS: At present, there is no robust scientific argument to formally contraindicate any of the standard treatments employed for headaches and neuralgias.