Antihyperalgesic effect of the N-methyl-D-aspartate receptor antagonist dextromethorphan in the oral surgery model

Peripheral neuronal barrage from tissue injury produces central nervous sys tem hyper excitability through the activation of N-methyl-D-aspartate (NMDA ) receptor sites by excitatory amino acids and neuropeptides. This study ev aluated if attenuation of NMDA receptor activation with dextromethorphan (D M) suppresses the postoperative development of hyperalgesia. Seventy-five-p atients undergoing oral surgery in a parallel-group, double-blind study ran domly received either a placebo or the maximally tolerated dose of DM admin istered orally prior to and continuing for 48 hours following surgery. Pain as measured by category, visual analog, and verbal descriptor scales was n ot significantly different between groups during the first 6 hours followin g surgery. However, pain at 48 hours was decreased in the DM group as measu red by scales for pain intensity and unpleasantness. Subjects in the DM gro up also self-administered fewer acetaminophen tablets for unrelieved pain o ver 24 to 48 hours postoperatively. The results suggest that DM at maximall y tolerated doses does not produce an analgesic effect in the immediate pos toperative period but reduces pain at 48 hours. This may be related to anta gonism of NMDA receptors necessary for the expression of hyperalgesia assoc iated with noxious afferent input postoperatively. (C) 1999 the American Co llege of Clinical Pharmacology.