Peripheral Metabotropic Glutamate Receptor Subtype 5 Contributes to Inflammation-Induced Hypersensitivity of the Rat Temporomandibular Joint

Abstract

Temporomandibular disorders (TMD) comprise an assortment of clinical conditions characterized by pain in the temporomandibular joint (TMJ). TMD patients have a variety of symptoms, including jaw movement disorder and TMJ pain. Metabotropic glutamate receptor subtype 5 (mGluR5) was reported to be involved in pain processing in several animal models of neuropathic and inflammatory pain. In this study, the head withdrawal threshold and mGluR5 expression were investigated in rats with complete Freund's adjuvant (CFA)-induced TMJ inflammatory pain. CFA injection into the TMJ significantly decreased the mechanical head withdrawal thresholds relative to vehicle injection, and the effects were blocked by pre-injection of 2-methyl-6-(phenylethynyl)-pyridine (MPEP). mGluR5 expression in the trigeminal ganglion was predominantly increased in the CFA-injected group compared with the normal control group. Pretreatment with MPEP, a selective mGluR5 antagonist, reduced mGluR5 expression in the trigeminal ganglion compared with the CFA group, as measured by immunohistochemistry, western blotting, and RT-PCR. Significant differences in the proportion or intensity of mGluR5 expression were found in animals with inflammation versus control animals at the examined time point. These findings indicate a role for peripheral mGluR5 in CFA-induced nociceptive behavior and TMJ inflammation. Peripheral application of mGluR5 antagonists could provide therapeutic benefits for inflammatory TMJ pain.