Background & Aims
Placebo hypoalgesia and nocebo hyperalgesia caused by directed expectations are well-established phenomena in the field of pain research (see e.g. Colloca & Barsky, 2020). Despite their recognition, the temporal stability of these expectation effects is rarely examined. There is evidence that placebo and nocebo effects are relatively persistent to extinction (Jepma et al., 2018; Whalley et al., 2008), in contrast to what would be expected if these effects could be exclusively accounted for by a simple prediction error model. In this study, we investigated the temporal stability of placebo and nocebo effects by testing the modulation of positive and negative expectations on pain in two sessions approximately one week apart. Additionally, EEG data were collected to test for neural patterns reflecting positive and negative expectations (Strube et al., 2021).
Methods
We invited 42 participants to take part in two sessions about a week apart. In the first session, verbal instructions and a conditioning procedure induced positive (placebo), negative (nocebo), or neutral (control) expectations for differently colored visual cues using sham neurofeedback. Expectations were not further reinforced in the second session. In both the first and second sessions, these expectations were then varied on a trial-by-trial basis (3 blocks of 30 trials each, for a total of 90 trials per session). In each trial, participants rated the expected and perceived intensity of an individually calibrated heat pain stimulus (VAS60) while EEG data were recorded. The intensity of the pain stimulus was always the same, independent of the cue.
Results
The expectation manipulation was successful, as indicated by expectation and pain ratings consistent with the cues on both days. In both sessions, the expectation effect (nocebo minus placebo) decreased over the three experimental blocks but did not differ between sessions. In contrast, pain effects were larger in the first session and decreased over the three blocks in both sessions, with a steeper decrease in the first session. Higher expectation effects in the first session predicted higher expectation effects in the second session, and similarly, pain effects in the first session predicted pain effects in the second session. Subjects who showed a greater decrease in expectation effects in the first session showed a smaller effect in the second session. EEG oscillatory activity during pain anticipation differed significantly between the placebo and nocebo conditions in the second session.
Conclusions
Our paradigm induced temporally stable behavioral effects of expectations on pain perception. The strength of the effects in the second session was predicted by the strength of the effects in the first session. Expectations were reflected in increased EEG oscillatory activity in the second session.
References
Colloca, L., & Barsky, A. J. (2020). Placebo and Nocebo Effects. The New England Journal of Medicine, 382(6), 554–561.
Jepma, M., Koban, L., van Doorn, J., Jones, M., & Wager, T. D. (2018). Behavioural and neural evidence for self-reinforcing expectancy effects on pain. Nature Human Behaviour, 2(11), 838-855
Strube, A., Rose, M., Fazeli, S., & Büchel, C. (2021). The temporal and spectral characteristics of expectations and prediction errors in pain and thermoception. Elife, 10, e62809.
Whalley, B., Hyland, M. E., & Kirsch, I. (2008). Consistency of the placebo effect. Journal of psychosomatic research, 64(5), 537-541.
Presenting Author
Maren-Isabel Wolf
Poster Authors
Maren-Isabel Wolf
M.Sc.
Institute of Systems Neuroscience, University Medical Center Hamburg-Eppendorf
Lead Author
Christoph Wittkamp
M.Sc.
Institute of Systems Neuroscience, University Medical Center Hamburg-Eppendorf
Lead Author
Michael Rose
PhD
Institute of Systems Neuroscience, University Medical Center Hamburg-Eppendorf
Lead Author
Topics
- Placebo