Thilo Friehs, Christopher Milde, Julia Anna Glombiewski, Tobias Kube

• Background Open-label placebos (OLP) prescribed without deception and with a convincing rationale have been shown to evoke powerful treatment effects. Patients’ treatment expectations seem to influence the magnitude of the effect. Objective We examined if two different OLP rationales increased pain tolerance and reduced pain intensity and unpleasantness in a standardized heat pain experiment. Methods Participants (N = 71) who self-reported reoccurring pain for at least the last 3 months were randomly assigned to one of three groups. We compared a personal-emotional and a scientific-matter-of-fact rationale with a control group (CG) that received the same placebo without any rationale. The rationale suggested a desensitizing effect on pain perception and improved pain coping of the placebo, whereas in the CG it was introduced as an ointment for measurement. The primary outcomes were pre–post changes in pain tolerance, expected and experienced pain intensity and unpleasantness. Results Participants showed a decrease in expected pain intensity, but not expected pain unpleasantness for both rationales. There were no differences in pain tolerance and experienced pain intensity and unpleasantness. Conclusions Our study suggests that evoking positive treatment expectations is not sufficient to elicit an OLP response. Possibly, the magnitude of expectations change in this study was not powerful enough to evoke an OLP effect. Additionally, it is possible that OLP effects in pain are unrelated to positive treatment expectations. The failure of OLP in our study is in contrast to a number of previous studies examining the effects of OLP in experimental and clinical pain. Significance This study provides evidence that positive treatment expectations are not sufficient to evoke an open-label placebo effect in a standardized heat pain experiment. We showed that two different rationales improved participants treatment expectations, but failed to evoke a placebo effect in comparison to a control group that received the same placebo, labelled as an ointment to improve measurement quality.