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Journal Articles Cell Reports Year : 2022

Diverse roles and modulations of IA in spinal cord pain circuits

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Nadine Clerc
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Abstract

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.

Dates and versions

hal-03871086 , version 1 (25-11-2022)

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Nadine Clerc, Aziz Moqrich. Diverse roles and modulations of IA in spinal cord pain circuits. Cell Reports, 2022, 38 (13), pp.110588. ⟨10.1016/j.celrep.2022.110588⟩. ⟨hal-03871086⟩
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