Papers of the Week

Neuropathic pain is caused by the lesion or disease of the somatosensory system and can be initiated and/or maintained by both central and peripheral mechanisms. Nerve injury leads to neuronal damage and apoptosis associated with the release of an array of pathogen- or damage-associated molecular patterns to activate inflammasomes. The activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome contributes to neuropathic pain and may represent a novel target for pain therapeutic development. In the current review, we provide an up-to-date summary of the recent findings on the involvement of NLRP3 inflammasome in modulating neuropathic pain development and maintenance, focusing on peripheral neuropathic conditions. Here we provide a detailed review of the mechanisms whereby NLRP3 inflammasomes contribute to neuropathic pain via (1) neuroinflammation, (2) apoptosis, (3) pyroptosis, (4) proinflammatory cytokine release, (5) mitochondrial dysfunction, and (6) oxidative stress. We then present the current research literature reporting on the antinociceptive effects of several natural products and pharmacological interventions that target activation, expression, and/or regulation of NLRP3 inflammasome. Furthermore, we emphasize the effects of microRNAs as another regulator of NLRP3 inflammasome. In conclusion, we summarize the possible caveats and future perspectives that might provide successful therapeutic approaches against NLRP3 inflammasome for treating or preventing neuropathic pain conditions.