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 system hyperexcitability through the activation of N-methyl-D-aspartate (NMDA) receptor sites by excitatory amino acids and neuropeptides. This study evaluated if attenuation of NMDA receptor activation with dextromethorphan (DM) suppresses the postoperative development of hyperalgesia. Seventy-five patients undergoing oral surgery in a parallel-group, double-blind study randomly received either a placebo or the maximally tolerated dose of DM administered orally prior to and continuing for 48 hours following surgery. Pain as measured by category, visual analog, and verbal descriptor scales was not significantly different between groups during the first 6 hours following surgery. However, pain at 48 hours was decreased in the DM group as measured by scales for pain intensity and unpleasantness. Subjects in the DM group also self-administered fewer acetaminophen tablets for unrelieved pain over 24 to 48 hours postoperatively. The results suggest that DM at maximally tolerated doses does not produce an analgesic effect in the immediate postoperative period but reduces pain at 48 hours. This may be related to antagonism of NMDA receptors necessary for the expression of hyperalgesia associated with noxious afferent input postoperatively.