Nav1.7 is expressed predominantly in nociceptive and sympathetic neurons. The role of this channel in nociceptive neurons has been characterized by human genetics, which indicates an essential and non-redundant role in pain transduction and conduction following noxious stimuli. Gain-of-function mutations have been described in Nav1.7 that result in extreme pain disorders such as inherited erythromelalgia (IEM), paroxysmal extreme pain disorder (PEPD) and SCN9A-associated small fiber neuropathy. In the disease states genetically linked to a gain-of-function of Nav1.7, the channel is mutated to increase the sodium influx resulting in a hyperexcitable sensory neuron, and a resultant sensation of pain.