Centrally expressed Cav3.2 T-type calcium channel is critical for the initiation and maintenance of neuropathic pain

  1. Sophie L Fayad
  2. Guillaume Ourties
  3. Benjamin Le Gac
  4. Baptiste Jouffre
  5. Sylvain Lamoine
  6. Antoine Fruquière
  7. Sophie Laffray
  8. Laila Gasmi
  9. Bruno Cauli
  10. Christophe Mallet
  11. Emmanuel Bourinet
  12. Thomas Bessaih
  13. Régis C Lambert  Is a corresponding author
  14. Nathalie Leresche
  1. Sorbonne University, CNRS, INSERM, France
  2. Université Clermont Auvergne, Inserm, France
  3. Université de Montpellier, CNRS, INSERM, France

Abstract

Cav3.2 T-type calcium channel is a major molecular actor of neuropathic pain in peripheral sensory neurons, but its involvement at the supra-spinal level is almost unknown. In the Anterior Pretectum (APT), a hub of connectivity of the somatosensory system involved in pain perception, we show that Cav3.2 channels are expressed in a sub-population of GABAergic neurons co-expressing parvalbumin (PV). In these PV-expressing neurons, Cav3.2 channels contribute to a high frequency bursting activity, which is increased in the spared nerve injury model of neuropathy. Specific deletion of Cav3.2 channels in APT neurons reduced both the initiation and maintenance of mechanical and cold allodynia. These data are a direct demonstration that centrally expressed Cav3.2 channels also play a fundamental role in pain pathophysiology.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Sophie L Fayad

    Sorbonne University, CNRS, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4834-6524
  2. Guillaume Ourties

    Université Clermont Auvergne, Inserm, Clermont-Ferrand, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Benjamin Le Gac

    Sorbonne University, CNRS, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Baptiste Jouffre

    Université Clermont Auvergne, Inserm, Clermont-Ferrand, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Sylvain Lamoine

    Université Clermont Auvergne, Inserm, Clermont-Ferrand, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Antoine Fruquière

    Université de Montpellier, CNRS, INSERM, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Sophie Laffray

    Université de Montpellier, CNRS, INSERM, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Laila Gasmi

    Sorbonne University, CNRS, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Bruno Cauli

    Sorbonne University, CNRS, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1471-4621
  10. Christophe Mallet

    Université Clermont Auvergne, Inserm, Clermont-Ferrand, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0873-6763
  11. Emmanuel Bourinet

    Université de Montpellier, CNRS, INSERM, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  12. Thomas Bessaih

    Sorbonne University, CNRS, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0764-7731
  13. Régis C Lambert

    Sorbonne University, CNRS, INSERM, Paris, France
    For correspondence
    regis.lambert@sorbonne-universite.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8972-1151
  14. Nathalie Leresche

    Sorbonne University, CNRS, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6705-9769

Funding

Agence Nationale de la Recherche (ANR-15-CE16-0012-03)

  • Emmanuel Bourinet

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All procedures complied with the ethical guidelines of the Federation for Laboratory Animal Science Associations (FELASA) and with the approval of the French National Consultative Ethics Committee for health and life sciences (authorization number: 17958).

Reviewing Editor

  1. Gary L Westbrook, Oregon Health & Science University, United States

Publication history

  1. Received: March 28, 2022
  2. Accepted: November 22, 2022
  3. Accepted Manuscript published: November 23, 2022 (version 1)

Copyright

© 2022, Fayad et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Sophie L Fayad
  2. Guillaume Ourties
  3. Benjamin Le Gac
  4. Baptiste Jouffre
  5. Sylvain Lamoine
  6. Antoine Fruquière
  7. Sophie Laffray
  8. Laila Gasmi
  9. Bruno Cauli
  10. Christophe Mallet
  11. Emmanuel Bourinet
  12. Thomas Bessaih
  13. Régis C Lambert
  14. Nathalie Leresche
(2022)
Centrally expressed Cav3.2 T-type calcium channel is critical for the initiation and maintenance of neuropathic pain
eLife 11:e79018.
https://doi.org/10.7554/eLife.79018
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