Psychopharmacology (Berl). 1983 ; 79(4): 325-8.

Opiate analgesia and its antagonism in dental event-related potentials: evidence for placebo antagonism.

Butler SH, Colpitts YH, Gagliardi GJ, Chen AC, Chapman CR.

The analgesic effects of the synthetic opiate fentanyl citrate (0.1 mg) on subjective pain reports (SPR) and late-wave event-related potentials (ERP) recorded during painful dental stimulation were examined in human subjects. Such waves have been shown to reflect the contribution of cognitive variables, such as expectancy and belief, to perception. In addition, the study was intended to demonstrate a dose-related narcotic antagonism with injection of naloxone (1.2 or 0.4 mg) or normal saline (double-blind) following IV fentanyl administration. Fentanyl reduced both ERP waveform amplitudes and SPR as have previously studied analgesic agents, such as nitrous oxide, acupuncture, and aspirin. Naloxone injection reversed both ERP and SPR changes, but surprisingly, a reversal of narcotic analgesia equal to that of 0.4 mg naloxone was seen with saline injection. By chance, all subjects were health-science students or professionals who were knowledgeable in opiate pharmacology, and so placebo reversal was hypothesized. Alternatively, it was hypothesized that fentanyl cleared more rapidly than predicted, thus, producing apparent reveal. In a second experiment involving similarly knowledgeable subjects with identical procedures and testing intervals, subjects received 0.1 mg fentanyl, but no reversal injection. The fentanyl effect was constant across this time period. The data, thus, support the hypothesis where the subjects were knowledgeable in opiate pharmacology, was placebo opiate antagonism.