NMDA receptor antagonists attenuate mechanical hyperalgesia in rats with unilateral inflammation of the hindpaw.

The effects of N-methyl-D-aspartate (NMDA) receptor antagonists on mechanical hyperalgesia associated with tissue inflammation were studied. Following an injection of the inflammatory agent, complete Freund's adjuvant, into the rat hindpaw, there was a significant decrease in threshold and an increase in response duration to mechanical stimuli, suggesting that a state of mechanical hyperalgesia was induced. The intrathecal administration of the NMDA receptor antagonists, dizocilpine maleate and (+/-)-2-amino-5-phosphonopentanoic acid, significantly increased mechanical threshold and reduced response duration in the inflamed hindpaw, but had no effect on the non-injected paw. The results suggest that NMDA receptor activation may contribute to the mechanical hyperalgesia that follows peripheral tissue inflammation.