EFFECT OF SYSTEMIC N-METHYL-D-ASPARTATE RECEPTOR ANTAGONIST (DEXTROMETHORPHAN) ON PRIMARY AND SECONDARY HYPERALGESIA IN HUMANS

Dextromethorphan is a non-competitive N-merhyl-D-aspartate (NMDA) rece ptor antagonist known to inhibit wind-up and central hyperexcitability of dorsal horn neurones. We studied 24 healthy, unmedicated male volu nteers, aged 21-28 yr, in a randomized, double-blind, placebo-controll ed, crossover study. Burn injuries were produced on the medial surface of the dominant calf with a 25x50 mm rectangular thermode. On three s eparate days, at least 1 week apart, subjects were given oral dextrome thorphan 60 mg, 120 mg or placebo. Dextromethorphan reduced the magnit ude of secondary hyperalgesia to pinprick but not to stroke. Dextromet horphan had no influence on primary hyperalgesia, pain during prolonge d noxious heat stimulation or heal pain detection thresholds in undama ged skin. Side effects were frequent but clinically acceptable. The ef fects of dextromethorphan were in agreement with experimental studies indicating that dextromethorphan is a NMDA receptor antagonist. The ef fects of dextromethorphan in the burn injury model were similar to tho se of ketamine and distinct from those of local anaesthetics and opioi ds.