Electrical signals in the small nerve fibres are (among others) generated by voltage-gated sodium channels. In about 15% of the patients with small fibre neuropathy a genetic change in the genes for these sodium channels especially the sodium channels Nav1.7, Nav1.8 and Nav1.9, can be found. The genes for these sodium channels are named SCN9A-, SCN10A- and SCN11A-gene. The genetic change causes a gain-of-function of the channel, making the channel hyperexcitable or hyperactive, which leads to the generation of pain signals without a physical pain stimulus. The sodium channelopathy may also cause autonomic dysfunction.

For genetic analysis a blood sample is needed. The analysis usually takes 2-3 months. Sometimes, it is uncertain whether a genetic change is the cause of the complaints. In that case, testing family members or functional tests may be needed to provide more certainty.