There are rare Mendelian pain disorders with extreme pain phenotypes such as inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEPD) because of monoallelic variants in SCN9a causing gain of function of the voltage-gated sodium channel NaV1.7.8,14,21,35,73 At a population level, neuropathic pain more commonly arises after disease or injury to the nervous system such as diabetic neuropathy, Herpes Zoster or trauma/surgery rather than a primary genetic cause. The gene discussed is SCN9A; the disease is paroxysmal extreme pain disorder.