P2Y2 Receptors Mediate Masseter Muscle Mechanical Hypersensitivity in Rats

Abstract

Purpose: P₂Y₂ receptors (P₂Y₂Rs) are among the various receptors that play an important role in nociception. The goal of this research was to investigate possible P₂Y₂R expression changes in the trigeminal ganglion (TRG) in bilateral masseter muscle (MM) hypersensitivity following unilateral MM inflammation. The impact of unilateral intramasseteric administration of P₂Y₂R antagonist on bilateral MM hypersensitivity was also explored. Materials and Methods: Bilateral MM hypersensitivity was provoked by unilateral intramasseteric injection of complete Freund’s adjuvant (CFA). The head withdrawal threshold (HWT) was assessed bilaterally 4 days later. Bilateral TRG and MM isolation were followed, and quantitative real-time polymerase chain reaction (qRT-PCR) and histopathological analysis were carried out on these tissues, respectively. The involvement of P₂Y₂Rs in nocifensive behavior was evaluated by administering two doses of P₂Y₂R antagonist AR-C118925 (0.2 or 1 mg/100 μL) in inflamed MM 4 days post-CFA administration. Bilateral HWT was assessed at different time points following antagonist injection. Results: qRT-PCR analysis demonstrated P₂Y₂R up-regulation in TRG ipsilateral to the site of CFA administration. Compared to the controls, both doses of AR-C118925 injected ipsilateral to the TRG increased the bilateral HWT at 30, 60, 90, and 120 minutes after antagonist administration. Conclusion: The findings suggest that P₂Y₂Rs may affect MM inflammatory hypersensitivity owing to its up-regulation in the TRG in MM inflammatory pain states.