Microglial P2X4 receptors are essential for spinal neurons hyperexcitability and tactile allodynia in male and female neuropathic mice

  • Damien Gilabert (Geteilte/r Erstautor/in)
  • Alexia Duveau (Geteilte/r Erstautor/in)
  • Sara Carracedo
  • Nathalie Linck
  • Adeline Langla
  • Rieko Muramatsu
  • Friedrich Koch-Nolte
  • François Rassendren
  • Thomas Grutter
  • Pascal Fossat
  • Eric Boué-Grabot (Geteilte/r Letztautor/in)
  • Lauriane Ulmann (Geteilte/r Letztautor/in)

Beteiligte Einrichtungen

Abstract

In neuropathic pain, recent evidence has highlighted a sex-dependent role of the P2X4 receptor in spinal microglia in the development of tactile allodynia following nerve injury. Here, using internalization-defective P2X4mCherryIN knockin mice (P2X4KI), we demonstrate that increased cell surface expression of P2X4 induces hypersensitivity to mechanical stimulations and hyperexcitability in spinal cord neurons of both male and female naive mice. During neuropathy, both wild-type (WT) and P2X4KI mice of both sexes develop tactile allodynia accompanied by spinal neuron hyperexcitability. These responses are selectively associated with P2X4, as they are absent in global P2X4KO or myeloid-specific P2X4KO mice. We show that P2X4 is de novo expressed in reactive microglia in neuropathic WT and P2X4KI mice of both sexes and that tactile allodynia is relieved by pharmacological blockade of P2X4 or TrkB. These results show that the upregulation of P2X4 in microglia is crucial for neuropathic pain, regardless of sex.

Bibliografische Daten

OriginalspracheEnglisch
ISSN2589-0042
DOIs
StatusVeröffentlicht - 17.11.2023

Anmerkungen des Dekanats

© 2023 The Author(s).

PubMed 37860691