Voltage Gated Sodium Channel Blockers: Potential Treatment for Neuropathic Pain

Voltage-gated sodium channels (VGSCs) in sensory neurons play a crucial role in neuropathic pain. Following nerve injury, alterations in the expression, distribution, kinetics and voltage-dependence of these sodium channels in sensory neurons can lead to alteration in initiation and propagation of electrical impulses in a way that contributes to enhance pain perception. Electrophysiological and pharmacological studies have revealed that specific sodium channel subtypes particularly Nav1.3, Nav1.7, Nav1.8 and Nav1.9 are predominantly expressed and involved in the peripheral nociceptive neurons associated pain signalling. Moreover, a human studies have shown that gain of function mutations in Nav1.7 lead to enhanced pain while loss of function mutations lead to complete insensitivity to pain. The clinical usefulness are limited by their off-target adverse effects. Development of subtype selective VGSCs blockers might be an effective approach for the treatment of neuropathic pain. This review will enlighten the role of sodium channels in neuropathic pain and development of newer subtype selective sodium channel blockers for neuropathic pain.