The finding of voltage-gated sodium channel mutations in small fibre neuropathy (with mutations in SCN9A, encoding for Nav1.7) being most frequently reported suggest a specific target for therapy.
Gain-of-function mutations in SCN9A gene that encodes the voltage-gated sodium channel NaV1.7 have been associated with a wide spectrum of painful syndromes in humans including inherited erythromelalgia, paroxysmal extreme pain disorder and small fibre neuropathy.
The Lacosamide-Efficacy-'N'-Safety in Small fiber neuropathy (LENSS) study is a randomized, double-blind, placebo-controlled, crossover trial in patients with SCN9A-associated small fiber neuropathy, with the primary objective to evaluate the efficacy of lacosamide versus placebo.
Recent studies have expanded this spectrum with gain-of-function SCN9A mutations in patients with small fiber neuropathy and in a new syndrome of pain, dysautonomia, and small hands and small feet (acromesomelia).
We sequenced all exons of SCN9A in 19 clinically well-studied cases including 6 CIP and 13 erythromelalgia (9 with family history, 10 with small-fibre neuropathy).
We recently reported missense substitutions in SCN9A that encode functional Na(v)1.7 variants in 28% of patients with biopsy-confirmed small fibre neuropathy.