Activation of peripheral group III metabotropic glutamate receptors inhibits pain transmission by decreasing neuronal excitability in the CFA-inflamed knee joint

Peripheral group III metabotropic glutamate receptors (mGluRs) function to modulate pain signaling in inflammatory states. Here, we established in vivo experimental settings, including dynamic weight bearing test and in vivo single nerve recording, to elucidate how the group III mGluRs contribute to inhibiting pain transmission at the peripheral sensory nerve terminal in inflammatory states (1 and 3 days) elicited by Complete Freund's Adjuvant (CFA). As a result, CFA-induced nociceptive behaviors were significantly alleviated after administration of 100 and 200 μM L-AP4 (l-2-amino-4-phosphonobutylate; group III mGluR agonist). In addition, neuronal discharges evoked by 6- and 26-g von Frey filaments at the nerve significantly decreased after administration of 200 μM L-AP4. However, this event was not observed in non-inflammatory state. These results suggest that the group III mGluRs negatively regulate nociceptive behavior and pain transmission by lessening neuronal firing rates at the peripheral nerve in inflammation.