Expression of CGRP in the Trigeminal Ganglion and Its Effect on the Polarization of Macrophages in Rats with Temporomandibular Arthritis

Abstract

Calcitonin gene-related peptide (CGRP) is synthesized and secreted by trigeminal ganglion neurons, and is a key neuropeptide involved in pain and immune regulation. This study investigates the expression of CGRP in the trigeminal ganglion (TG) and its regulatory role in the polarization of macrophages in rats with temporomandibular arthritis. A rat model of temporomandibular arthritis was established using CFA. Pain behavior was then observed. Temporomandibular joint (TMJ) and the TG were collected, and immunohistochemistry, immunofluorescence (IF) staining, and RT-qPCR were used to examine the expression of CGRP and macrophage-related factors. To investigate the impact of CGRP on macrophage polarization, both CGRP and its antagonist, CGRP 8-37, were separately administered directly within the TG. Statistical analysis revealed that within 24 h of inducing temporomandibular arthritis using CFA, there was a significant surge in CD86 positive macrophages within the ganglion. These macrophages peaked on the 7th day before beginning their decline. In this context, it’s noteworthy that administering CGRP to the trigeminal ganglion can prompt these macrophages to adopt the M2 phenotype. Intriguingly, this study demonstrates that injecting the CGRP receptor antagonist (CGRP 8-37) to the ganglion counteracts this shift towards the M2 phenotype. Supporting these in vivo observations, we found that in vitro, CGRP indeed fosters the M2-type polarization of macrophages. CGRP can facilitate the conversion of macrophages into the M2 phenotype. The phenotypic alterations of macrophages within the TG could be instrumental in initiating and further driving the progression of TMJ disorders.