The Next Generation of Non-Opioid Analgesics for Neuropathic Pain

Neuropathic pain affects an estimated 7 to 10 percent of the global population and remains one of the most treatment-resistant pain conditions in clinical medicine. First-line pharmacotherapies, including gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors, provide meaningful relief for only a minority of patients, and opioids carry well-documented risks that have reshaped prescribing practice worldwide. A 2025 Lancet Neurology systematic review underscored the modest and inconsistent efficacy of existing pharmacological options across neuropathic pain subtypes. At the same time, the January 2025 FDA approval of suzetrigine, a selective Nav1.8 sodium channel blocker, marked a genuine inflection point: the first mechanistically distinct, non-opioid analgesic approved for moderate-to-severe acute pain in over two decades, opening a credible path toward peripherally targeted agents for chronic neuropathic conditions.The pipeline behind suzetrigine is broad and active. Voltage-gated sodium channels Nav1.7 and Nav1.8, TRP channels including TRPV1, TRPA1, and TRPM3, potassium channel modulators, and targets within neuroinflammatory cascades, among them CGRP signaling and glial activation pathways, are all under serious preclinical and clinical investigation. Gene therapy approaches aimed at silencing pain-relevant sodium channels are advancing in parallel. Despite this momentum, translating target validation into effective, well-tolerated therapies for neuropathic pain specifically remains difficult. Heterogeneity across neuropathic pain etiologies, the complexity of central sensitization, and the persistent gap between animal model findings and human trial outcomes continue to slow progress. This Research Topic invites contributions that address these challenges directly: studies characterizing novel analgesic targets, mechanistic work elucidating peripheral and central sensitization in neuropathic conditions, preclinical efficacy and safety data for emerging compounds, and translational or clinical studies evaluating non-opioid strategies across diabetic neuropathy, chemotherapy-induced peripheral neuropathy, postherpetic neuralgia, and other defined subtypes.We welcome original research articles, systematic reviews and meta-analyses, clinical trials, and focused narrative reviews. Thematic areas of particular interest include selective ion channel pharmacology, biologics and monoclonal antibodies targeting pain mediators, gene and RNA-based therapeutic approaches, neuroimmune mechanisms driving neuropathic states, biomarker development for patient stratification, and the design of clinical trials that better capture neuropathic pain heterogeneity. Work spanning the full translational arc, from target discovery through early-phase clinical evaluation, is encouraged. The goal of this collection is to map where the science is genuinely moving and to create a reference point for researchers working to close the gap between promising mechanisms and treatments patients can actually use. Topic editors: Cristian Acosta, Mohammad-Reza Ghovanloo Source: https://www.frontiersin.org/research-topics/84372/the-next-generation-of-non-opioid-analgesics-for-neuropathic-pain