The N-methyl-D-aspartate receptor antagonist dextromethorphan selectively reduces temporal summation of second pain in man.

Oral doses of dextromethorphan (DM), a common cough suppressant and N-methyl-D-aspartate (NMDA) receptor antagonist, and their vehicle control were given on a double-blind basis to normal volunteer human subjects who rated intensities of first and second pain in response to repeated painful electric shocks and repeated 52 degrees C heat pulses. Doses of 30 and 45 mg, but not 15 mg, were effective in attenuating temporal summation of second pain, a psychophysical correlate of temporal summation of C afferent-mediated responses of dorsal horn nociceptive neurons, termed 'wind-up'. By contrast, neither first nor second pain evoked by the first stimulus in a train of stimuli were affected by any of these doses of DM. These results further confirm temporal summation of second pain as a psychophysical correlate of wind-up by providing evidence that DM selectively reduces temporal summation of second pain, as has been shown for wind-up.