EXCITATORY AMINO-ACID RECEPTOR INVOLVEMENT IN PERIPHERAL NOCICEPTIVE TRANSMISSION IN RATS

The involvement of excitatory amino acid receptors in peripheral nocic eptive processing was assessed in two separate experiments. In the fir st, one knee joint cavity of rats was injected with 0.1 mi of L-glutam ate (0.001 mM; 0.1 mM; 1.0 mM), L-aspartate (0.001 mM; 0.1 mM; 1.0 mM) , L-arginine (0.1 mM) or different combinations of these amino acids. The animals tested for paw withdrawal latency to radiant heat and with drawal threshold to von Frey filaments at different time points. Combi nations of glutamate/aspartate, aspartate/areinine or glutamate/aspart ate/arginine when injected into the joint, in the absence of any other treatment, reduced the paw withdrawal latency and withdrawal threshol d immediately after the injection and persisting up to 5 h indicating the development of hyperalgesia and allodynia. Subsequent intra-articu lar injection of either an NMDA or a non-NMDA glutamate receptor antag onist ((+/-)-2-amino-7-phosphonoheptanoic acid (AP7), 0.2 mM) or 6-cya no-7-nitroquinoxaline-2,3-dione (CNQX), 0.1 mM) attenuated the thermal hyperalgesia and the mechanical allodynia produced by glutamate/aspal tate/arginine. On the other hand, in a second experiment intra-articul ar injection of AP7, ketamine or CNQX reversed the hyperalgesia and al lodynia produced by injection of a mixture of kaolin and carrageenan i nto the joint. These receptor antagonists, however, did not have an ef fect on the joint edema. These findings provide evidence for a potenti al role of peripheral NMDA and non-NMDA receptors in nociceptive trans mission. (C) 1997 Elsevier Science B.V.