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 paroxysmal extreme pain disorder.