Voltage-gated sodium channel (Nav) (Nav)

Voltage-gated sodium channels (Nav) in peripheral neurons, specifically the Nav1.7, Nav1.8, and Nav1.9 subtypes, are essential proteins for the initiation and propagation of electrical signals in the peripheral nervous system [Source: Nature Reviews Neuroscience, 2013]. These channels are primarily expressed in nociceptors within the dorsal root ganglia and are responsible for transmitting pain signals from the periphery to the central nervous system. Nav1.7 acts as a threshold setter, Nav1.8 contributes significantly to the action potential upstroke, and Nav1.9 regulates resting membrane potential and excitability [Source: The Lancet Neurology, 2014]. Mutations in the genes encoding these channels (SCN9A, SCN10A, SCN11A) are directly linked to human pain disorders, such as erythromelalgia and congenital insensitivity to pain, making them high-value targets for analgesic development. Therapeutic strategies focus on developing isoform-selective inhibitors, such as the Nav1.8-selective blocker suzetrigine, to provide effective pain relief while minimizing side effects associated with non-selective sodium channel inhibition in the heart or brain [Source: New England Journal of Medicine, 2024]. By targeting channels localized to the peripheral nervous system, researchers aim to avoid the dose-limiting toxicities of traditional sodium channel blockers like lidocaine or carbamazepine. Overall, peripheral Nav channels represent a validated and promising class of targets for the next generation of non-opioid pain management therapies.

Other names

Nav1.7Nav1.8Nav1.9SCN9ASCN10ASCN11APeripheral sodium channelSodium channel protein type 9 subunit alphaSodium channel protein type 10 subunit alphaSodium channel protein type 11 subunit alphaPN1SNS

Inhibition of sodium ion influx through the alpha-subunit pore of the channel, which prevents membrane depolarization and the subsequent generation and conduction of action potentials in peripheral sensory neurons [Source: Nature Reviews Drug Discovery, 2018].