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

Damien Gilabert, Alexia Duveau, Sara Carracedo, Nathalie Linck, Adeline Langla, Rieko Muramatsu, Friedrich Koch-Nolte, François Rassendren, Thomas Grutter, Pascal Fossat, Eric Boué-Grabot, Lauriane Ulmann
iScience. 2023-11-01; 26(11): 108110
DOI: 10.1016/j.isci.2023.108110

Lire sur PubMed

Gilabert D(1)(2), Duveau A(3), Carracedo S(3), Linck N(1)(2), Langla A(3), Muramatsu R(4), Koch-Nolte F(5), Rassendren F(1)(2), Grutter T(6), Fossat P(3), Boué-Grabot E(3), Ulmann L(1)(2).

Author information:
(1)IGF, University Montpellier, CNRS, INSERM, F-34094 Montpellier, France.
(2)LabEx Ion Channel Science and Therapeutics, Montpellier, France.
(3)University Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France.
(4)Department of Molecular Pharmacology, National Institute of Neuroscience,
National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan.
(5)Institute of Immunology, University Medical Center Hamburg-Eppendorf, D-20246
Hamburg, Germany.
(6)University of Strasbourg, CNRS, CAMB UMR 7199, F-67000 Strasbourg, France.

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.

© 2023 The Author(s).

DOI: 10.1016/j.isci.2023.108110
PMCID: PMC10583052
PMID: 37860691

Conflict of interest statement: The authors declare no competing interests.

Auteurs Bordeaux Neurocampus