Role of T CD4+ cells, macrophages, C-low threshold mechanoreceptors and spinal Cav3.2 channels in inflammation and related pain-like symptoms in murine inflammatory models - Université Clermont Auvergne Accéder directement au contenu
Article Dans Une Revue British Journal of Pharmacology Année : 2023

Role of T CD4+ cells, macrophages, C-low threshold mechanoreceptors and spinal Cav3.2 channels in inflammation and related pain-like symptoms in murine inflammatory models

Amaury François
Emmanuel Bourinet

Résumé

Background and purpose: T-type calcium channels, mainly the Cav 3.2 subtype, are important contributors to the nociceptive signaling pathway. We investigated their involvement in inflammation and related pain-like symptoms. Experimental approach: The involvement of Cav 3.2 and T-type channels was investigated using genetic and pharmacological inhibition to assess mechanical allodynia/hyperalgesia and edema development in two murine inflammatory pain models. The location of Cav 3.2 involved in pain-like symptoms was studied in mice with Cav 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-edematous effect of Cav 3.2 inhibition was investigated in chimeric mice with immune cells deleted for Cav 3.2. Lymphocytes and macrophages from either green fluorescent protein-targeted Cav 3.2 or KO mice were used to determine the expression of Cav 3.2 protein and the functional status of the cells. Key results: We showed the role of Cav 3.2 channels in the development of pain-like symptoms and edema in the two murine inflammatory pain models. For the first time, we provide evidence of the involvement of Cav 3.2 channels located on C-LTMRs and spinal cord in inflammatory pain. We showed that Cav 3.2 channels located in T cells and macrophages contribute to the inflammatory process. Conclusion and implications: This work highlights the crucial role of Cav 3.2 channels in inflammation and related pain and suggests that targeting Cav 3.2 channels with pharmacological agents could be an attractive and readily evaluable strategy in a clinical trial to relieve chronic inflammatory pain in affected patients.
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Dates et versions

hal-03790651 , version 1 (28-09-2022)

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Elodie Picard, Nicolas Kerckhove, Amaury François, Ludivine Boudieu, Elisabeth Billard, et al.. Role of T CD4+ cells, macrophages, C-low threshold mechanoreceptors and spinal Cav3.2 channels in inflammation and related pain-like symptoms in murine inflammatory models. British Journal of Pharmacology, 2023, 180 (4), pp.385-400. ⟨10.1111/bph.15956⟩. ⟨hal-03790651⟩
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