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) receptor antagonist known to inhibit wind-up and central hyperexcitability of dorsal horn neurones. We studied 24 healthy, unmedicated male volunteers, aged 21-28 yr, in a randomized, double-blind, placebo-controlled, crossover study. Burn injuries were produced on the medial surface of the dominant calf with a 25x50 mm rectangular thermode. On three separate days, at least 1 week apart, subjects were given oral dextromethorphan 60 mg, 120 mg or placebo. Dextromethorphan reduced the magnitude of secondary hyperalgesia to pinprick but not to stroke. Dextromethorphan had no influence on primary hyperalgesia, pain during prolonged noxious heat stimulation or heal pain detection thresholds in undamaged skin. Side effects were frequent but clinically acceptable. The effects of dextromethorphan were in agreement with experimental studies indicating that dextromethorphan is a NMDA receptor antagonist. The effects of dextromethorphan in the burn injury model were similar to those of ketamine and distinct from those of local anaesthetics and opioids.