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

Behavioral neuroscience Biological sciences Natural sciences Neuroscience Pathophysiology Physiology Sensory neuroscience

Journal

iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038

Informations de publication

Date de publication:
17 Nov 2023
Historique:
received: 12 06 2023
revised: 25 08 2023
accepted: 28 09 2023
medline: 20 10 2023
pubmed: 20 10 2023
entrez: 20 10 2023
Statut: epublish

Résumé

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

Identifiants

pubmed: 37860691
doi: 10.1016/j.isci.2023.108110
pii: S2589-0042(23)02187-9
pmc: PMC10583052
doi:

Types de publication

Journal Article

Langues

eng

Pagination

108110

Informations de copyright

© 2023 The Author(s).

Déclaration de conflit d'intérêts

The authors declare no competing interests.

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Auteurs

Damien Gilabert (D)

IGF, University Montpellier, CNRS, INSERM, F-34094 Montpellier, France.
LabEx Ion Channel Science and Therapeutics, Montpellier, France.

Alexia Duveau (A)

University Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France.

Sara Carracedo (S)

University Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France.

Nathalie Linck (N)

IGF, University Montpellier, CNRS, INSERM, F-34094 Montpellier, France.
LabEx Ion Channel Science and Therapeutics, Montpellier, France.

Adeline Langla (A)

University Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France.

Rieko Muramatsu (R)

Department of Molecular Pharmacology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan.

Friedrich Koch-Nolte (F)

Institute of Immunology, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany.

François Rassendren (F)

IGF, University Montpellier, CNRS, INSERM, F-34094 Montpellier, France.
LabEx Ion Channel Science and Therapeutics, Montpellier, France.

Thomas Grutter (T)

University of Strasbourg, CNRS, CAMB UMR 7199, F-67000 Strasbourg, France.

Pascal Fossat (P)

University Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France.

Eric Boué-Grabot (E)

University Bordeaux, CNRS, IMN, UMR 5293, F-33000 Bordeaux, France.

Lauriane Ulmann (L)

IGF, University Montpellier, CNRS, INSERM, F-34094 Montpellier, France.
LabEx Ion Channel Science and Therapeutics, Montpellier, France.

Classifications MeSH