Influence of the method of drug administration on analgesic response

The appropriate control group in studies of placebo-induced analgesia has not been established. A traditional control has been a 'no treatment' or natural-history group. In some studies, the natural-history group receives a hidden infusion of vehicle, a physiologically inactive substance such as saline solution, to eliminate differences in expectation of the outcome on the part of the experimenter. To evaluate whether 'hidden' as well as open infusion of vehicle can elicit a placebo response, we have now tested a different natural-history group, one which received an infusion of vehicle from a syringe pump controlled by a programmable timer. A comparison of these two control groups provides evidence that hidden infusion of vehicle can elicit a placebo response. Use of this new control group also permitted a clear distinction between a naloxone-antagonizable component of placebo analgesia and naloxone antagonism of endorphin-mediated analgesia induced by surgical stress. Our study underscores the power of the placebo and emphasizes that even the most subtle cues can elicit a placebo response.