NLRP3 inflammasome: a key driver of neuroinflammation and a novel therapeutic target for neuropathic pain.

Abstract

Neuropathic pain represents a serious complication arising from a spectrum of disorders that precipitate lesions within the central and peripheral nervous systems. This disabling pain can persist for years, severely diminishing the quality of life of the affected individuals. The treatment options available for neuropathic pain at present have limited efficacy. Moreover, the adverse effects associated with these options restrict their application. The exact etiological mechanisms underlying the pathogenesis of neuropathic pain remain unclear. However, neuroinflammatory processes mediated by the immune system play significant roles in the initiation and progression of neuropathic pain in various models. The nucleotide-binding domain and leucine-rich repeat pyrin-containing protein-3 (NLRP3) inflammasome, a pivotal element of the innate immune system, plays an indispensable role in the pathophysiological mechanisms of central and peripheral neuropathic pain. However, the precise mechanisms facilitating its activation in disparate neuropathic pain conditions remain to be elucidated. Gaining insights into the regulatory mechanisms affecting NLRP3 inflammasome activation in diverse neuropathic pain-associated disorders will aid in developing novel therapeutic avenues. Therefore, this review summarizes the current knowledge on the role of the NLRP3 inflammasome in the pathophysiology of several neuropathic pain-related conditions, such as diabetic neuropathic pain, chemotherapy-induced neuropathic pain, peripheral nerve compression, central nervous system neuropathic pain, radiculopathy, and morphine analgesic tolerance. In addition, this review also discusses the possible use of this inflammasome as a therapeutic target to alleviate the pain-related symptoms of these diseases.