Middleton, Steven J, Perini, Irene, Themistocleous, Andreas C, Weir, Greg A, McCann, Kirsty, Barry, Allison M, Marshall, Andrew 
ORCID: 0000-0001-8273-7089, Lee, Michael, Mayo, Leah M, Bohic, Manon et al (show 14 more authors)
(2022)
Na(v)1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice.
BRAIN, 145 (10).
pp. 3637-3653.
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | affective touch, C-low threshold mechanoreceptors, congenital insensitivity to pain, Na(v)1, 7 |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 11 Jan 2022 16:33 |
| Last Modified: | 18 Jan 2023 21:16 |
| DOI: | 10.1093/brain/awab482 |
| Open Access URL: | https://doi.org/10.1093/brain/awab482 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3146240 |
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