Sodium channel protein type 7 subunit alpha (Nav1.7) and Sodium channel protein type 8 subunit alpha (Nav1.8) (Nav1.7 and Nav1.8)

Sodium channel protein type 7 subunit alpha (Nav1.7) and sodium channel protein type 8 subunit alpha (Nav1.8) are two key voltage-gated sodium channels predominantly expressed in peripheral sensory neurons, especially dorsal root ganglion (DRG) nociceptors. Nav1.7 acts as a threshold channel, setting the excitability of nociceptors and is highly sensitive to tetrodotoxin (TTX); mutations in Nav1.7 are linked to inherited pain syndromes such as erythromelalgia. Nav1.8 is TTX-resistant, is crucial for action potential propagation in nociceptors, and is upregulated in chronic inflammatory pain states. Both channels are validated targets for pain therapy: selective inhibitors or modulators could provide non-opioid, non-addictive pain relief with potentially fewer CNS side effects. Major therapeutic challenges remain regarding isoform selectivity and clinical efficacy, but research efforts are ongoing.

Other names

Voltage-gated sodium channel alpha subunit 7Voltage-gated sodium channel alpha subunit 8SCN9ASCN10ATTX-sensitive sodium channelTTX-resistant sodium channel

Drugs block sodium influx by inhibiting channel opening, reducing neuron excitability (channel blockade). Toxins or compounds can modify channel kinetics and inactivation (gating modulation). Partial inhibition, particularly for Nav1.8, can reverse hyperexcitability without complete channel shutdown. The therapeutic strategy often involves subtype selectivity, targeting only peripheral Nav channels to avoid CNS side effects or addiction.