Background & Aims

Pain can be modulated by positive and negative expectations (Benedetti et al., 2022; Colloca & Barsky, 2020). While the effects of positive expectations (placebo analgesia) are well researched, little is known regarding the behavioral and neural effects of negative expectations on pain processing (nocebo hyperalgesia). Furthermore, more research is needed to identify shared and distinct mechanisms underlying both of these effects in the same paradigm and in the same individual. This preregistered study investigates neural mechanisms how positive and negative treatment expectations are being acquired and how they influence the processing of nociceptive information and the subjective perception of pain in healthy volunteers.

Methods

We investigate the temporal dynamics and neural mechanisms underlying the formation and effects of positive and negative expectations in an established model of conditioned placebo hypoalgesia/nocebo hyperalgesia (Colloca et al., 2010) using a within-subject design and functional magnetic resonance imaging (fMRI). Sixty-five participants will complete two phases: 1) expectation formation during conditioning with experimental reinforcement of positive or negative treatment experience and 2) a placebo/nocebo test session without such reinforcement. The main outcomes are neural (BOLD) responses, expectancy ratings, and pain ratings to cued thermal pain stimuli. Furthermore, exploratory outcome measures, their association with individual expectations and their effects on pain (placebo/nocebo effects) will be assessed. These include psychological state/trait measures, functional/structural brain connectivity (resting-state fMRI, DTI, etc.), and genetics.

Results

The data collection is currently being finalized (46 out of 65 participants collected, anticipated end of data collection April 2024) and first results will be presented at the IASP meeting. On the behavioral level, we hypothesize stronger nocebo hyperalgesia than placebo hypoalgesia effects as well as a faster and stronger formation of negative expectations as compared to positive expectations over time. On the neural level, we hypothesize changes in BOLD activity and connectivity in the placebo/nocebo condition compared to the control condition – in prefrontal, mesolimbic, and pain-related brain areas.

Conclusions

This study will shed light on the shared and distinct (neural) mechanisms underlying positive and negative expectations, and their influence on pain processing. Importantly, the study will reveal new insights into the formation and time course of positive and negative expectations.

References

Benedetti, F., Frisaldi, E., & Shaibani, A. (2022). Thirty years of neuroscientific investigation of placebo and nocebo: the interesting, the good, and the bad. Annual Review of Pharmacology and Toxicology, 62, 323-340.

Colloca, L., & Barsky, A. J. (2020). Placebo and nocebo effects. New England Journal of Medicine, 382(6), 554-561.

Colloca, L., Petrovic, P., Wager, T. D., Ingvar, M., & Benedetti, F. (2010). How the number of learning trials affects placebo and nocebo responses. Pain, 151(2), 430-439.

Presenting Author

Helena Hartmann

Poster Authors

Helena Hartmann

PhD

University Hospital Essen

Lead Author

E-mail

Katharina Schmidt

PhD

University Hospital Essen

Lead Author

E-mail

Angelika Kunkel

PhD

University Hospital Essen

Lead Author

E-mail

Katja Wiech

University of Oxford

Lead Author

E-mail

Ulrike Bingel

University Duisburg-Essen, University Hospital

Lead Author

E-mail

Topics

  • Pain Imaging