Direct comparison of placebo effects on clinical and experimental pain

Objectives: Placebo effects have been suggested to be more potent on clinical than experimental pain. However, this proposition is based on the comparison of the magnitude of placebo analgesia between studies using different methodologies or between different groups of subjects within the same study. The authors sought to provide a more direct test of this hypothesis using a within-subject design and to investigate the potential mediating effect of expectancy Method: Sixteen patients with low back pain rated the intensity and the unpleasantness of their clinical pain and underwent two cold pressor tests, both before and after a saline injection presented either as a potent painkiller (placebo treatment) in one session or as an inactive substance in a control session. Results: The placebo treatment produced comparable increases in expected relief for clinical and experimental pain. However, ratings of pain intensity, pain unpleasantness, and perceived relief confirmed the larger placebo effect in low back pain than cold pressor pain. Retrospective ratings of perceived relief in low back pain generally showed the largest placebo effect compared with concurrent pain ratings. Furthermore, when the placebo session was performed after the control session, the placebo effect on low back pain was substantially reduced and observed only in perceived relief. Variations in expectation could not account for the large difference in placebo analgesia between clinical and experimental pain. Conclusions: The important reduction in placebo analgesia in low back pain after the single pre-exposure to the ineffective control treatment suggests the additional involvement of highly flexible mechanisms that may counteract the pro-analgesic effects of expectations.