Expectations of analgesia do not affect spinal nociceptive R-III reflex activity: an experimental study into the mechanism of placebo-induced analgesia

The purpose of this study was to investigate whether placebo analgesia is m ediated by the release of beta-endorphin. In addition to subjective pain re ports, we included an objective physiological parameter of nociception refl ected by the opioid sensitive nociceptive R-III reflex. Placebo consisted o f strong suggestions of pain relief and an intravenous injection of saline. Forty minutes after placebo, either the opioid antagonist naloxone or sali ne was administered intravenously without subjects noticing (hidden). Sixty healthy males, aged 18-30 years, voluntarily participated in this study. S ubjects were randomized into one of four groups: group 1 received placebo a nd hidden naloxone, group 2 received hidden naloxone only, group 3 received placebo and hidden saline and group 4 received hidden saline only. Pain wa s induced by electrical stimulation of the sural nerve and evaluated with a visual analogue scale (VAS). In addition, changes in the magnitude of the nociceptive R-III reflex activity were assessed. We determined to what exte nt R-III reflex activity and subjective pain reports were decreased by plac ebo and we investigated whether these placebo-induced changes in reflex act ivity and subjective pain reports were naloxone reversible. Furthermore, we measured the degree of association between pain relief as measured on VAS and changes in R-III reflex activity. Finally, the role of beta-endorphin w as assessed by measuring plasma endorphin levels before and after the admin istration of placebo. This study could not demonstrate a placebo effect as measured on VAS and R-III responses. The administration of placebo did not appear to have an effect on the release of beta-endorphins. Consistently, t he antagonizing effects of naloxone were negligible. A subgroup analysis of those who did show a placebo response as indicated on the VAS did not supp ort the supposition that beta-endorphin is released due to placebo suggesti on. It is suggested that intensified stimuli and a more effective procedure to induce placebo analgesia (e.g. conditioning) may produce a proper place bo effect. (C) 2000 International Association for the Study of Pain. Publis hed by Elsevier Science B.V. All rights reserved.