Christophe Mallet

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.