Meta-analysis of neural systems underlying placebo analgesia from individual participant fMRI data

TY - JOUR

T1 - Meta-analysis of neural systems underlying placebo analgesia from individual participant fMRI data

AU - Zunhammer, Matthias

AU - Spisák, Tamás

AU - Wager, Tor D

AU - Bingel, Ulrike

AU - Placebo Imaging Consortium

AU - Keßner, Simon

PY - 2021/3/2

Y1 - 2021/3/2

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-021-21179-3

DO - 10.1038/s41467-021-21179-3

M3 - SCORING: Journal article

C2 - 33654105

VL - 12

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

M1 - 1391

ER -