Voltage-gated sodium channel Nav1.7 and Nav1.8 (Nav1.7/Nav1.8)

Voltage-gated sodium channels Nav1.7 and Nav1.8 are critical transmembrane proteins primarily expressed in the peripheral nervous system, specifically within the dorsal root ganglia and nociceptive neurons. Nav1.7, encoded by the SCN9A gene, acts as a 'threshold setter' that amplifies small depolarizations to trigger action potentials, while Nav1.8, encoded by SCN10A, is responsible for the majority of the inward current during the upstroke of the action potential in specialized pain-sensing fibers (Source: UniProt Q15858, Q9Y5Y9). These channels play a fundamental role in the transmission of pain signals from the periphery to the spinal cord. Mutations in the genes encoding these channels are linked to severe pain disorders, such as erythromelalgia, or the complete absence of pain perception, making them highly validated targets for analgesic drug development (Source: NIH GeneReviews NBK1116). Therapeutic strategies focus on developing isoform-selective inhibitors, such as suzetrigine, to provide potent pain relief without the dose-limiting side effects associated with non-selective sodium channel blockers like lidocaine or the addiction risks of opioids (Source: NEJM 2024;390:1189-1199).

Other names

Sodium channel protein type 9 subunit alphaSodium channel protein type 10 subunit alphaSCN9ASCN10APN1PN3Peripheral nerve sodium channels

These targets are inhibited by selective or non-selective small molecule blockers that bind to the alpha subunit of the channel, preventing the influx of sodium ions. This stabilization of the resting state or blockade of the pore inhibits the initiation and conduction of action potentials in nociceptive neurons, thereby reducing the transmission of pain signals to the central nervous system (Source: PubMed PMC6110131, StatPearls NBK540971).