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

•We evaluated effects of peripheral group II and III mGluR on arthritic pain of rats.•Pain behavior is relevant with reduced weight bearing and mechanical hyperalgesia.•Pre-treatment of group II and III mGluR agonist attenuated nociceptive behavior.•Post-treatment of group II and III mGluR agonist attenuated nociceptive behavior. 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 30. min before (induction phase) and 4. h after (maintenance phase) the injection of carrageenan (1%, 50. μl).During the induction phase of arthritic pain, a significant recovery of reduced weight load occurred after the administration of 500. μM APDC ((2R, 4R)-4-aminopyrrolidine-2,4-dicarboxylate; group II agonist) and 100 and 500. μM L-AP4 (. l-2-amino-4-phosphonobutylate; group III agonist). Similarly, 100 and 500. μM APDC and 500. μM L-AP4 significantly reduced mechanical hyperalgesia during the induction phase. In the maintenance phase, APDC at all doses (10, 100 and 500. μM) and 100 and 500. μM L-AP4 significantly counteracted the reduction in weight load, and APDC and L-AP4 at all doses (10, 100 and 500. μM) 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.