Ondansetron does not inhibit the analgesic effect of alfentanil

5-Hydroxytryptamine (5-HT) causes antinociception via presynaptic 5-HT3 (5-HT subtype 3) receptors on primary afferent nociceptive neurones in the spinal cord dorsal horn. Therefore, ondansetron (a 5-HT3 receptor antagonist) may increase the perception of a noxious stimulus or decrease the effects of concurrently administered antinociceptive drugs. Using a randomized, double-blind, crossover study design, we have tested this hypothesis in eight healthy volunteers who, on three different days, received either ondansetron and placebo, ondansetron and alfentanil or placebo and alfentanil. Experimental pain was induced with heat, cold, mechanical pressure and electrical stimulation. Ondansetron alone did not change the response to any of the experimental tests, but alfentanil and the combination ondansetron-alfentanil significantly changed the response compared with ondansetron alone. There was no difference between alfentanil alone and the combination ondansetron-alfentanil. We conclude that ondansetron does not change the response to pressure, heat, cold or electrical nociceptive stimuli or antagonize the analgesic effect of alfentanil.