Gain-of-function mutations in the gene encoding the α subunit of NaV1.7 (SCN9A) underlie two painful neuropathies known as paroxysmal extreme pain disorder (PEPD) and inherited erythromelalgia (IE) [66,67], whereas loss-of-function mutations in SCN9A result in a congenital indifference to all forms of pain [68,69]. This evidence concerns the gene SCN9A and paroxysmal extreme pain disorder.