Safety and Tolerability of Lacosamide in Patients With Gain-of-function Nav1.7 Mutations Related Small Fiber Neuropathy

Lacosamide is a functionalized amino acid with antinociceptive properties in inflammatory and neuropathic pain, and displays a unique mechanism: it enhances slow inactivation of Nav1.3, Nav1.7, and Nav1.8. Nav1.7 is expressed predominantly in nociceptive and sympathetic neurons. Gain-of-function mutations have been described in Nav1.7 that result in extreme pain disorders such as SCN9A-associated small fiber neuropathy. In the disease states genetically linked to a gain-of-function of Nav1.7, the sodium channel is mutated to increase the sodium influx resulting in a hyperexcitable sensory neuron, and a resultant sensation of pain. The objective of the study is to determine the efficacy and safety of lacosamide, a sodium channel blocker, in patients with pain due to SCN9A-associated small fiber neuropathy.