Role of T CD4 ⁺ cells, macrophages, C-low threshold mechanoreceptors and spinal Ca v 3.2 channels in inflammation and related pain-like symptoms in murine inflammatory models.

Publisher: Wiley Country of Publication: England NLM ID: 7502536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5381 (Electronic) Linking ISSN: 00071188 NLM ISO Abbreviation: Br J Pharmacol Subsets: MEDLINE

Publication: London : Wiley
Original Publication: London, Macmillian Journals Ltd.

Inflammation* ; Chronic Pain*; Mice ; Animals ; Hyperalgesia ; CD4-Positive T-Lymphocytes ; Mechanoreceptors ; Macrophages

Background and Purpose: T-type calcium channels, mainly the Ca v 3.2 subtype, are important contributors to the nociceptive signalling pathway. We investigated their involvement in inflammation and related pain-like symptoms.
Experimental Approach: The involvement of Ca v 3.2 and T-type channels was investigated using genetic and pharmacological inhibition to assess mechanical allodynia/hyperalgesia and oedema development in two murine inflammatory pain models. The location of Ca v 3.2 channels involved in pain-like symptoms was studied in mice with Ca v 3.2 knocked out in C-low threshold mechanoreceptors (C-LTMR) and the use of ABT-639, a peripherally restricted T-type channel inhibitor. The anti-oedema effect of Ca v 3.2 channel inhibition was investigated in chimeric mice with immune cells deleted for Ca v 3.2. Lymphocytes and macrophages from either green fluorescent protein-targeted Ca v 3.2 or KO mice were used to determine the expression of Ca v 3.2 protein and the functional status of the cells.
Key Results: Ca v 3.2 channels contributed to the development of pain-like symptoms and oedema in the two murine inflammatory pain models. Our results provided evidence of the involvement of Ca v 3.2 channels located on C-LTMRs and spinal cord in inflammatory pain. Ca v 3.2 channels located in T cells and macrophages contribute to the inflammatory process.
Conclusion and Implications: Ca v 3.2 channels play crucial roles in inflammation and related pain, implying that targeting of Ca v 3.2 channels with pharmacological agents could be an attractive and readily evaluable strategy in clinical trials, to relieve chronic inflammatory pain in patients.
(© 2022 British Pharmacological Society.)

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ANR-15-CE16-0012-01 Agence Nationale de la Recherche; Centre National de la Recherche Scientifique; European Fund for Regional Economic Development; Fondation pour la Recherche Médicale; Institut National de la Santé et de la Recherche Médicale; Université Clermont-Auvergne; Université de Montpellier; équipe FRM 2015 FRM; Pack Ambition Recherche 2021 regional council of Auvergne-Rhône-Alpes; Société Française d'Etude et de Traitement de la Douleur; 16-IDEX-0001CAP20-25 Agence Nationale de la Recherche ''Investissements d'Avenir''

Keywords: T-type calcium channels; inflammation; inflammatory pain; mechanical hypersensitivity; pharmacology

Date Created: 20220922 Date Completed: 20230113 Latest Revision: 20230210

20240513

10.1111/bph.15956

36131381