Introduction: Erythromelalgia (EM) is a rare neurovascular peripheral nerve disorder caused by mutation of the Na⁺ channel gene SCN9A. Patients experience severe burning pain and skin redness whenever exposed to high temperatures.
Objective: To investigate the pathophysiology of EM using threshold tracking techniques.
Methods: Multiple excitability measures: strength-duration time constant (SDTC), threshold electrotonus, and the recovery of excitability were recorded in 7 (SCN9A gene identified) patients with primary EM. In an additional series, heating was applied to investigate symptoms generation with temperature change.
Results: At rest, EM patients showed longer SDTC (a marker of persistent Na⁺ channels) compared to controls. However, in a single subject, when temperature was raised from 32^oC to 37.8^oC, SDTC increased significantly with a reduction in the accommodation to depolarizing current and reduced refractory periods. These changes were consistent in sensory and motor recordings. These findings support the hypothesis that changes in Na⁺ channel function reflect underlying SCN9A mutations. Strikingly, these results were opposite to those delivered when heating controls (Kiernan et al., 2001) which decreased the relative refractory period by 7.8% per ^oC, slowed the accommodation to depolarizing currents and decreased SDTC by 2.6%.
Conclusions: This is the first study of primary EM undertaken using threshold tracking techniques, demonstrating significant differences in Na⁺-channel dependent parameters between EM patients with SCN9A mutation and controls. There were paradoxical changes in parameters with heating in comparison to controls. These preliminary findings support the use of excitability techniques as a biomarker of abnormalities of Na_v1.7 sodium channel in-vivo.