Peripheral group II and III metabotropic glutamate receptors in the knee joint attenuate carrageenan-induced nociceptive behavior in rats

Abstract

This study sought to evaluate whether peripheral group II and III metabotropic glutamate receptors (mGluRs) in the knee joint have inhibitory effects on carrageenan-induced nociceptive behavior. To this end, changes in weight load and hind paw withdrawal threshold were measured in rats following the administration of specific peripheral group II and III mGluR agonists 30min before (induction phase) and 4h after (maintenance phase) the injection of carrageenan (1%, 50μl). During the induction phase of arthritic pain, a significant recovery of reduced weight load occurred after the administration of 500μM APDC ((2R, 4R)-4-aminopyrrolidine-2,4-dicarboxylate; group II agonist) and 100 and 500μM L-AP4 (l-2-amino-4-phosphonobutylate; group III agonist). Similarly, 100 and 500μM APDC and 500μM L-AP4 significantly reduced mechanical hyperalgesia during the induction phase. In the maintenance phase, APDC at all doses (10, 100 and 500μM) and 100 and 500μM L-AP4 significantly counteracted the reduction in weight load, and APDC and L-AP4 at all doses (10, 100 and 500μM) inhibited mechanical hyperalgesia. The current study suggests that peripheral group II and III mGluRs in the knee joint negatively modulates nociceptive behavior during both the induction and maintenance phases of carrageenan-induced arthritic pain.