Rare inherited channelopathies show a crucial role of VGSC in pain processing (Bennett and Woods 2014; Hoeijmakers et al. 2015); loss-of-function mutations in Nav1.7 are associated with insensitivity to pain (Cox et al. 2006), while gain-of-function mutations in Nav1.7 lead to hyperexcitability and pain disorders in humans, erythromelalgia and paroxysmal extreme pain disorder (Estacion et al. 2008). This evidence concerns the gene SCN9A and channelopathy.