Nav1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice

Steven Middleton , Irene Perini , Andreas Themistocleous , Greg Weir , Kirsty Mccann , Allison Barry , Andrew Marshall , Michael Lee , Leah Mayo , Manon Bohic , Georgios Baskozos , India Morrison , Line Löken , Sarah Mcintyre , Saad Nagi , Roland Staud , Isac Sehlstedt , Richard Johnson , Johan Wessberg , John Wood , Christopher Woods , Aziz Moqrich (1) , Håkan Olausson , David Bennett

1 IBDM - Institut de Biologie du Développement de Marseille

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 electromyography (n = 3 CIP participants and n = 8 healthy controls), we found that these patients also have abnormalities in the encoding of affective touch, which is mediated by the specialized 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.

Domaines: Sciences du Vivant [q-bio]

Steven Middleton, Irene Perini, Andreas Themistocleous, Greg Weir, Kirsty Mccann, et al.. Nav1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice. Brain - A Journal of Neurology , 2022, 145 (10), pp.3637-3653. ⟨10.1093/brain/awab482⟩. ⟨hal-03871087⟩