Centrally administered non-NMDA but not NMDA receptor antagonists block peripheral knee joint inflammation.

An experimental arthritis of the knee joint resulted in limping, guarding, and an increased response to heat stimuli (heat hyperalgesia). Spinal administration of the non-N-methyl-D-aspartate (non-NMDA) antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), significantly reduced the degree of peripheral inflammation, thermal and behavioral manifestations of arthritis. NMDA antagonists had no effect on the inflammation but did prevent the development of the heat hyperalgesia. Thus, central non-NMDA receptors play a major role in the development of peripheral inflammation while both non-NMDA and NMDA receptors are involved in the development of heat hyperalgesia.