Sodium channel protein type 9 subunit alpha and Sodium channel protein type 10 subunit alpha (NaV1.7 and NaV1.8) (NaV1.7/NaV1.8)

Voltage-gated sodium channels NaV1.7 and NaV1.8, encoded by the SCN9A and SCN10A genes, are essential components of the electrical signaling machinery in peripheral sensory neurons. These channels are highly expressed in nociceptors within the dorsal root ganglia and trigeminal ganglia, where they play distinct but complementary roles in pain perception [1][2]. NaV1.7 serves as a “threshold setter” that amplifies small generator potentials to trigger action potentials, while NaV1.8 is responsible for the majority of the sodium current during the action potential's rising phase, especially under conditions of inflammation or nerve injury [3][4]. Human genetic evidence strongly validates these targets; for instance, loss-of-function mutations in SCN9A lead to congenital insensitivity to pain, whereas gain-of-function mutations cause debilitating chronic pain syndromes like erythromelalgia [5][6]. Pharmacological targeting of these channels aims to achieve high selectivity to avoid interfering with NaV1.5 in the heart or NaV1.1/1.2 in the brain, which can cause arrhythmias or seizures [7]. Recent advancements include the development of selective inhibitors like suzetrigine (VX-548), which has demonstrated efficacy in clinical trials for acute and neuropathic pain by blocking signal transmission specifically in the peripheral nervous system [8][9].

Other names

SCN9ASCN10APN1PN3SNSPeripheral nerve sodium channelsVoltage-gated sodium channel type IX alpha subunitVoltage-gated sodium channel type X alpha subunit

Selective or non-selective inhibition of the alpha subunit of voltage-gated sodium channels NaV1.7 and NaV1.8, preventing the influx of sodium ions and thereby inhibiting the initiation and conduction of action potentials in nociceptive sensory neurons.