In addition, some of the electrophysiologically confirmed NaV1.7-associated PEPD (p.V1298F, p.V1299D) and PE (p.P1308L, p.V1316A) mutations [5, 18, 37, 57] as well as one NaV1.9 mutation (p.V1184A) causing cold-aggravated peripheral pain [42] are located in or near the DIII S4/S5 linker, further emphasizing the disease-relevance of alteration p.V1287I in NaV1.8. Here, SCN10A is linked to paroxysmal extreme pain disorder.