Meta-analysis of neural systems underlying placebo analgesia from individual participant fMRI data
Matthias Zunhammer, Tamás Spisák, Tor D. Wager, Ulrike Bingel, Lauren Y. Atlas, Fabrizio De Benedetti, Christian Büchel, Jae Chan Choi, Luana Colloca, Davide Duzzi, Falk Eippert, Dan‐Mikael Ellingsen, Sigrid Elsenbruch, Stephan Geuter, Ted J. Kaptchuk, Simon S. Kessner, Irving Kirsch, Jian Kong, Claus Lamm, Siri Leknes, Fausta Lui, Alexa Huber, Carlo Adolfo Porro, Markus Rütgen, Lieven A. Schenk, Julia Schmid, Nina Theysohn, Irene Tracey, Nathalie Wrobel, Fadel Zeidan
Abstract
The brain systems underlying placebo analgesia are insufficiently understood. Here we performed a systematic, participant-level meta-analysis of experimental functional neuroimaging studies of evoked pain under stimulus-intensity-matched placebo and control conditions, encompassing 603 healthy participants from 20 (out of 28 eligible) studies. We find that placebo vs. control treatments induce small, widespread reductions in pain-related activity, particularly in regions belonging to ventral attention (including mid-insula) and somatomotor networks (including posterior insula). Behavioral placebo analgesia correlates with reduced pain-related activity in these networks and the thalamus, habenula, mid-cingulate, and supplementary motor area. Placebo-associated activity increases occur mainly in frontoparietal regions, with high between-study heterogeneity. We conclude that placebo treatments affect pain-related activity in multiple brain areas, which may reflect changes in nociception and/or other affective and decision-making processes surrounding pain. Between-study heterogeneity suggests that placebo analgesia is a multi-faceted phenomenon involving multiple cerebral mechanisms that differ across studies.