To determine whether both the N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the knee joint contribute to the induction and/or maintenance of arthritic pain, we examined the effects of intra-articular injection of NMDA receptor antagonist dizocilpine (MK-801) and non-NMDA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo[f]quinoxaline (NBQX) on the decrease in weight load induced by carrageenan injection into the knee joint cavity in rats. Injection of MK-801 (0.75 and 1.5 mM) and NBQX (0.25, 0.625 and 2.5 mM) immediately prior to carrageenan injection (2%, 40 microl) significantly prevented the pain-related behavior. However, injection of MK-801 (0.75 and 1.5 mM) and NBQX (0.625 and 2.5 mM) 5 h after carrageenan injection had no effect on pain-related behavior. These results suggest that both the NMDA and non-NMDA receptors in the knee joint are involved in the induction, but not maintenance, of arthritic pain.