Nav1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice - Archive ouverte HAL Access content directly
Journal Articles Brain - A Journal of Neurology Year : 2022

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

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

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-03871087 , version 1 (25-11-2022)

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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⟩
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