Targeting connexins: possible game changer in managing neuropathic pain?

Neuropathic pain is a chronic debilitating condition caused by nerve injury or a variety of diseases. At the core of neuropathic pain lies the aberrant neuronal excitability in the peripheral and/or central nervous system (PNS and CNS). Enhanced connexin expression and abnormal activation of connexin-assembled gap junctional channels are prominent in neuropathic pain along with reactive gliosis, contributing to neuronal hypersensitivity and hyperexcitability. In this review, we delve into the current understanding of how connexin expression and function contribute to the pathogenesis and pathophysiology of neuropathic pain and argue for connexins as potential therapeutic targets for neuropathic pain management.