Sodium channel protein type 10 subunit alpha (NaV1.8) and Sodium channel protein type 11 subunit alpha (NaV1.9) (NaV1.8/NaV1.9)

Voltage-gated sodium channels NaV1.8 and NaV1.9 are critical components of the peripheral nervous system, primarily localized in the nociceptive neurons of the dorsal root and trigeminal ganglia [2, 14]. These channels are characterized by their resistance to tetrodotoxin (TTX) and their specialized roles in the generation and propagation of pain signals [3, 5]. NaV1.8 is essential for the upstroke of action potentials during repetitive firing in nociceptors, while NaV1.9 regulates the resting membrane potential and amplifies subthreshold stimuli, thereby lowering the threshold for pain [14, 20]. Dysregulation or mutations in the genes encoding these channels, SCN10A and SCN11A, are associated with various painful conditions, including small fiber neuropathy, erythromelalgia, and inflammatory pain [7, 16]. Due to their restricted expression in peripheral sensory neurons, they are considered high-value targets for the development of selective, non-opioid analgesics [1, 11]. Drugs like suzetrigine (VX-548) and VX-150 aim to provide effective pain relief by selectively inhibiting these channels, potentially avoiding the systemic and addictive side effects associated with traditional pain medications like opioids [7, 13].

Other names

SCN10ASCN11APN3PN5SNSNaNSNS-2hPN3hNaNPeripheral nerve sodium channel 3Peripheral nerve sodium channel 5Sensory neuron-specific sodium channel

Selective inhibition of the alpha subunits of NaV1.8 and NaV1.9 voltage-gated sodium channels to reduce the excitability of peripheral nociceptors and block the transmission of pain signals.