Na_v1.7

Na_V1.7, encoded by SCN9A, is a voltage-gated sodium channel strongly linked to human nociception, because loss-of-function mutations cause congenital inability to experience pain^[1]. Mechanistically, Na_V1.7 supports nociceptor excitability and pain signaling, and human studies show that Na_V1.7 loss can produce a profound loss of functional nociceptors^[2]. In disease models and inherited pain syndromes, gain-of-function SCN9A mutations are associated with paroxysmal extreme pain disorder and related painful phenotypes^[3]. Compared with related isoforms, human dorsal root ganglion neurons show higher Na_V1.7 expression and lower Na_V1.8 expression than mouse dorsal root ganglion neurons, which is relevant for translational pain research^[4]. For experimental applications, inflammatory mediators such as NGF and IL-6 sensitize adult dorsal root ganglion neurons, and combined Na_V1.7/Na_V1.8 blockade strongly affects thermally evoked firing^[5]. Structural studies of Na_V1.7 antagonists map drug-binding sites and support rational inhibitor design^[6].