Title :

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

Author(s) :

Picard, Elodie [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Institut Analgesia
Neuro-Dol [Neuro-Dol]
Kerckhove, Nicolas [Auteur]
CHU Clermont-Ferrand
Institut Analgesia
Neuro-Dol [Neuro-Dol]
François, Amaury [Auteur]
Institut de Génomique Fonctionnelle [IGF]
Boudieu, Ludivine [Auteur]
Institut Analgesia
Neuro-Dol [Neuro-Dol]
Billard, Elisabeth [Auteur]
Université Clermont Auvergne [UCA]
Carvalho, Frédéric Antonio [Auteur]
Institut Analgesia
Neuro-Dol [Neuro-Dol]
Bogard, Gemma [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Gosset, Philippe [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Bourdier, Justine [Auteur]
Institut Analgesia
Neuro-Dol [Neuro-Dol]
Aissouni, Youssef [Auteur]
Institut Analgesia
Neuro-Dol [Neuro-Dol]
Bourinet, Emmanuel [Auteur]
Institut de Génomique Fonctionnelle [IGF]
Eschalier, Alain [Auteur]
Institut Analgesia
Neuro-Dol [Neuro-Dol]
Daulhac, Laurence [Auteur]
Institut Analgesia
Neuro-Dol [Neuro-Dol]
Mallet, Christophe [Auteur correspondant]
Institut Analgesia
Neuro-Dol [Neuro-Dol]

Journal title :

British Journal of Pharmacology

Pages :

385-400

Publisher :

Wiley

Publication date :

2023

ISSN :

0007-1188

English keyword(s) :

T-type calcium channels
inflammation
inflammatory pain
mechanical hypersensitivity
pharmacology

HAL domain(s) :

Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]/Immunologie
Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC]

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

ANR Project :

Une approche genetique pour elucider le role des canaux calciques de type-T dans la douleur neuropathique
Canaux ioniques d'intérêt thérapeutique

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL