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An international research consortium led by the University of Duisburg-Essen analysed brain imaging data from 16 studies involving 409 participants and found that different placebo induction methods engage distinct neural mechanisms. The study was published in Nature Communications on 17 July 2026.
Placebo effects rely on an individual’s expectation of pain relief, which can be shaped in two different ways. In one approach, participants receive verbal information suggesting that a treatment will reduce pain. In the other, verbal suggestions are combined with conditioning, allowing participants to directly experience pain relief during a learning phase (placebo analgesia).
Until now, it remained unclear whether different ways of generating placebo effects rely on the same biological mechanisms. A new study published in Nature Communications now provides compelling evidence that they do not.
Researchers from the Collaborative Research Center/Transregio 289 Treatment Expectation at University Medicine Essen, together with the international Placebo Imaging Consortium, analyzed brain imaging data from 409 participants in 16 studies on placebo-related pain relief. Their findings reveal that placebo pain relief induced by verbal suggestion alone and placebo analgesia strengthened by learning from experience rely on overlapping but partly distinct neural pathways,
"Because placebo studies can differ widely in their experimental details, it has been difficult to identify the brain processes they have in common," says Prof. Tamas Spisak, first author of the study and researcher at University Medicine Essen. "By combining participant-level data from many laboratories around the world, we were able to show that some of this heterogeneity is actually informative. Different placebo induction methods leave distinct signatures in the brain, and large collaborative datasets allow us to uncover these patterns."
The findings were made possible through the Placebo Imaging Consortium, an international collaboration established to share neuroimaging data and expertise across laboratories studying placebo effects.
"By identifying distinct neural pathways, we move closer to understanding which mechanisms are engaged in different clinical situations," says Prof. Ulrike Bingel, neurologist, spokesperson of CRC/TRR 289 Treatment Expectation, and senior author of the study. "In the future, this knowledge may help us develop more targeted strategies to support patients' own pain-relieving systems and optimize treatment outcomes."
The researchers emphasize that placebo effects are not simply imagined improvements. Rather, they are accompanied by measurable changes in brain activity that alter how pain is processed and experienced.
Prof. Dr. med. Ulrike Bingel, Speaker, CRC/TRR 289 Treatment Expectation, University Medicine Essen, ulrike.bingel@uk-essen.de
Prof. Dr. Tamas Spisak, Center for Translational Neuro- and Behavioral Sciences, University Medicine Essen, tamas.spisak@uk-essen.de
https://www.nature.com/articles/s41467-026-74743-0
https://www.uni-due.de/med/meldung.php?id=1972 Detailed research press release
https://treatment-expectation.de/en TRR 289 – Treatment Expectation
Prof. Ulrike Bingel is Professor of Neurology at the University of Duisburg-Essen's Faculty of Medic ...
Copyright: DGN/Andre Zelck
Prof. Tamas Spisak is a researcher at University Medicine Essen and first author of the study. Toget ...
Copyright: UDE/ Bettina Engel-Albustin
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