ObjectiveThe predelivery of intravenous alfentanil (a &mgr; opioid agonist) and ketamine (anN-methyl d-aspartate antagonist) has recently been shown to decrease the secondary hyperalgesia induced by intradermal capsaicin. The focus of this study was to determine the effects of the postdelivery of intravenous alfentanil and ketamine on intradermal capsaicin–induced secondary hyperalgesia.DesignDouble-blind, placebo-controlled, randomized, crossover study. Five minutes after an intradermal capsaicin injection, alfentanil and ketamine infusions were administered for a target plasma concentration of 75 ng/ml for alfentanil and 150 ng/ml for ketamine or placebo equivalent using a computer-controlled infusion pump and maintained for the remainder of the study. The investigator recorded the magnitude of the pain score at the time of injection and at 5-minute intervals. Fifteen minutes after the intradermal capsaicin injection, the region of secondary hyperalgesia and flare response was determined.ResultsAlfentanil and ketamine plasma levels targeted after injection of intradermal capsaicin had no significant effect on pain scores, flare response, or secondary hyperalgesia.ConclusionsConsistent with animal studies on preemptive analgesia, this study demonstrates that alfentanil and ketamine have a differential effect when delivered before and after a painful stimulus. Because of the differential effect seen, future studies on the pharmacology of human experimental pain should evaluate both predrug and postdrug delivery.