Neuropathic Pain: the Dysfunction of Drp1, Mitochondria, and ROS Homeostasis.

Neuropathic pain affects the physical and mental health status of patients. Due to its complex pathogenesis and the adverse reactions to medicines, its treatment remains challenging. Among all the etiologies, increasing evidence has pointed to mitochondrial dysfunction. Dynamin-related protein 1 (Drp1)-mediated mitochondrial fragmentation leads to excess ROS generation, which is implicated in the pathogenesis of neuropathic pain. However, the exact mechanism remains unclear. Studies aiming to clarify the possible pathway and relationship between Drp1, mitochondria, ROS, and neuropathic pain may identify a good treatment for neuropathic pain in the clinic. As shown in this review, dysfunction of Drp1 and ROS homeostasis plays essential roles in neuropathic pain. We summarized a Drp1-mitochondrial fission-ROS cycle that potentially functions in neuropathic pain and is regulated by posttranslational modifications and Ca2+. Additionally, we further enumerated six Drp1 inhibitors, including Mdivi-1, P110, Drp1 antisense oligodeoxynucleotides, hyperbaric oxygen, melatonin, and β-hydroxybutyrate, as potential treatments, with the aim of providing guidance for novel molecules to be used in the clinic.