Peripheral voltage-gated sodium channel (Peripheral VGSC)

Voltage-gated sodium channels (VGSCs) in peripheral sensory neurons, specifically the Nav1.7, Nav1.8, and Nav1.9 isoforms, are essential for the transmission of pain signals from the periphery to the central nervous system [1, 2, 4]. These channels are primarily expressed in nociceptors within the dorsal root and trigeminal ganglia [6, 11]. Nav1.7 acts as a threshold channel that amplifies generator potentials to trigger action potentials, while Nav1.8 and Nav1.9 are responsible for the upstroke and maintenance of these signals, particularly under pathological conditions [2, 4, 6]. Mutations in the genes encoding these channels (SCN9A, SCN10A, SCN11A) lead to various pain disorders, including erythromelalgia and congenital insensitivity to pain [5, 10, 17]. Due to their localized expression, they are prime targets for developing non-opioid analgesics that avoid central nervous system and cardiac side effects [6, 10]. Therapeutic approaches include non-selective blockers like lidocaine and newer, isoform-selective inhibitors such as the Nav1.8-selective blocker suzetrigine [8, 13].

Other names

Nav1.7Nav1.8Nav1.9SCN9ASCN10ASCN11ANociceptor-specific sodium channelsTTX-resistant sodium channelsTTX-sensitive sodium channelsPeripheral sodium channels

Voltage-gated sodium channel inhibition, Sodium channel blockade