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

Background and Purpose T‐type calcium channels, mainly the Cav3.2 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 Cav3.2 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 Cav3.2 channels involved in pain‐like symptoms was studied in mice with Cav3.2 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 Cav3.2 channel inhibition was investigated in chimeric mice with immune cells deleted for Cav3.2. Lymphocytes and macrophages from either green fluorescent protein‐targeted Cav3.2 or KO mice were used to determine the expression of Cav3.2 protein and the functional status of the cells. Key Results Cav3.2 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 Cav3.2 channels located on C‐LTMRs and spinal cord in inflammatory pain. Cav3.2 channels located in T cells and macrophages contribute to the inflammatory process. Conclusion and Implications Cav3.2 channels play crucial roles in inflammation and related pain, implying that targeting of Cav3.2 channels with pharmacological agents could be an attractive and readily evaluable strategy in clinical trials, to relieve chronic inflammatory pain in patients. ▪