Placebo pp 37-69 | Cite as

A Meta-analysis of Brain Mechanisms of Placebo Analgesia: Consistent Findings and Unanswered Questions

  • Lauren Y. AtlasEmail author
  • Tor D. Wager
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 225)


Placebo treatments reliably reduce pain in the clinic and in the lab. Because pain is a subjective experience, it has been difficult to determine whether placebo analgesia is clinically relevant. Neuroimaging studies of placebo analgesia provide objective evidence of placebo-induced changes in brain processing and allow researchers to isolate the mechanisms underlying placebo-based pain reduction. We conducted formal meta-analyses of 25 neuroimaging studies of placebo analgesia and expectancy-based pain modulation. Results revealed that placebo effects and expectations for reduced pain elicit reliable reductions in activation during noxious stimulation in regions often associated with pain processing, including the dorsal anterior cingulate, thalamus, and insula. In addition, we observed consistent reductions during painful stimulation in the amygdala and striatum, regions implicated widely in studies of affect and valuation. This suggests that placebo effects are strongest on brain regions traditionally associated with not only pain, but also emotion and value more generally. Other brain regions showed reliable increases in activation with expectations for reduced pain. These included the prefrontal cortex (including dorsolateral, ventromedial, and orbitofrontal cortices), the midbrain surrounding the periaqueductal gray, and the rostral anterior cingulate. We discuss implications of these findings as well as how future studies can expand our understanding of the precise functional contributions of the brain systems identified here.


Placebo effect Placebo response Expectancy Pain fMRI PET Opioid Prefrontal cortex Periaqueductal gray Amygdala Meta-analysis MKDA Neuroimaging 



This work was supported in part by the Intramural Research program of the NIH’s National Center for Complementary and Alternative Medicine.


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© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.National Center for Complementary and Alternative MedicineNational Institutes of HealthBethesdaUSA
  2. 2.Departments of Psychology and NeuroscienceUniversity of ColoradoBoulderUSA

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