Small fiber neuropathy (SFN) is a relatively common disorder of peripheral nerves, primarily affecting small somatic fibers, autonomic fibers, or both. In a proportion of patients with SFN, no underlying cause can be identified; these cases are termed idiopathic SFN. Gain-of-function mutations in SCN9A have recently been reported to be present in 28% of patients with idiopathic SFN, suggesting an underlying genetic basis for a proportion of patients with this disease. Electrophysiological analysis demonstrated multiple gain-of-function changes in the mutant channels with each of the mutations resulting in hyperexcitability in dorsal root ganglion (DRG) neurons. Moreover, most of these mutations showed impaired slow inactivation of Nav1.7, a finding that provides a rationale to evaluate the possible pain reduction potential of lacosamide in this condition.