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

Voltage-gated sodium channels NaV1.7 and NaV1.8 are essential proteins in the peripheral nervous system responsible for the initiation and propagation of pain signals [1.1.2, 1.3.5]. NaV1.7, encoded by the SCN9A gene, acts as a 'threshold channel' that amplifies small stimuli to trigger action potentials, while NaV1.8, encoded by SCN10A, is a tetrodotoxin-resistant channel that sustains high-frequency firing during inflammation [1.2.2, 1.4.2]. These channels are primarily expressed in the dorsal root ganglia (DRG), making them attractive targets for non-opioid analgesics that minimize central nervous system side effects [1.2.2, 1.3.1]. 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 severe chronic pain syndromes like erythromelalgia [1.4.3, 1.3.4]. Recent therapeutic advances include the development of highly selective inhibitors like suzetrigine (VX-548), which specifically targets NaV1.8 to treat acute and neuropathic pain [1.2.1, 1.2.2]. Despite their promise, achieving high subtype selectivity remains a challenge to avoid off-target effects on cardiac (NaV1.5) or central (NaV1.1/1.2) sodium channels [1.1.2, 1.2.1].

Other names

SCN9ASCN10AVoltage-gated sodium channel NaV1.7Voltage-gated sodium channel NaV1.8PN1PN3Peripheral sodium channel 1Sensory neuron-specific sodium channel

Selective inhibition of NaV1.7 and/or NaV1.8 to block the initiation and propagation of pain signals in peripheral sensory neurons.