Nav1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice
Middleton SJ., Perini I., Themistocleous AC., Weir GA., McCann K., Barry AM., Marshall A., Lee M., Mayo LM., Bohic M., Baskozos G., Morrison I., Löken LS., McIntyre S., Nagi SS., Staud R., Sehlstedt I., Johnson RD., Wessberg J., Wood JN., Woods CG., Moqrich A., Olausson H., Bennett DL.
Abstract Patients with bi-allelic loss of function mutations in the voltage-gated sodium channel Nav1.7 present with congenital insensitivity to pain (CIP), whilst low threshold mechanosensation is reportedly normal. Using psychophysics (n = 6 CIP participants and n = 86 healthy controls) and facial EMG (n = 3 CIP participants and n = 8 healthy controls) we have found that these patients also have abnormalities in the encoding of affective touch which is mediated by the specialised afferents; C-low threshold mechanoreceptors (C-LTMRs). In the mouse we found that C-LTMRs express high levels of Nav1.7. Genetic loss or selective pharmacological inhibition of Nav1.7 in C-LTMRs resulted in a significant reduction in the total sodium current density, an increased mechanical threshold and reduced sensitivity to non-noxious cooling. The behavioural consequence of loss of Nav1.7 in C-LTMRs in mice was an elevation in the von Frey mechanical threshold and less sensitivity to cooling on a thermal gradient. Nav1.7 is therefore not only essential for normal pain perception but also for normal C-LTMR function, cool sensitivity and affective touch.