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Cited by 162Pain Management and Placebo EffectPain Mechanisms and TreatmentsPain Management and Treatment

A meta-analysis of brain mechanisms of placebo analgesia: consistent findings and unanswered questions

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Atlas, Lauren Y., Wager, Tor D.·2014·Handbook of Experimental Pharmacology
DOI 10.1007/978-3-662-44519-8_3PMC PMC7671088
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Abstract

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.

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  • All parts of insula (posterior, mid and anterior) as well as cACC may be regulated by top-down systems during processing of bottom-up interoceptive input and processing of top-down induced activation in the interoceptive stream.

    “While it is not clear to what extent early interoceptive signals are prone to modulation, it has been shown that all parts of insula (posterior, mid and anterior) as well as cACC may be regulated by top-down systems during processing of bottom-up interoceptive input (Atlas and Wager, 2014) and processing of top-down induced activation in the interoceptive stream (Singer et al., 2006; Rutgen et al.”

    From Top-Down Dysregulation—From ADHD to Emotional Instability (2016) · cites this paper as Atlas and Wager, 2014

    The Results section (page unavailable) reports expectancy-associated reductions during noxious stimulation in anterior, middle, and left posterior insula and dorsal anterior cingulate cortex. This supports modulation during pain processing, but the paper does not establish that all posterior insula or the specifically named caudal ACC is regulated during bottom-up interoceptive processing generally. The later clause about top-down-induced activation is attached to other citations, not this one. (LLM, conf=0.82)

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  • lOFC has been activated in several placebo treatment studies, often in co-activation with rACC.

    “The lOFC has been activated in several placebo treatment studies (often in co-activation with rACC) as indicated by meta-analysis (Atlas and Wager, 2014; Wager and Atlas, 2015; Figure 6A) including placebo analgesia (Petrovic et al., 2002; Lieberman et al., 2004; Wager et al., 2004) and emotional placebo (Petrovic et al., 2005).”

    From Top-Down Dysregulation—From ADHD to Emotional Instability (2016) · cites this paper as Atlas and Wager, 2014

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Authors
Atlas, L. Y., & Wager, T. D.
Affiliations
  • National Institutes of Health (US)
  • University of Colorado Boulder (US)
Corresponding author
Atlas, Lauren Y.
ORCID
Venue
Handbook of Experimental Pharmacology
Publisher
Springer Berlin Heidelberg
Published
2014
Volume
225
Pages
37-69
ISSN
  • 0171-2004 (ISSN-L)
  • 1865-0325
DOI
10.1007/978-3-662-44519-8_3
PMC
PMC7671088
OpenAlex
W19718613
Cited by
162
References
123
Citations by year
2026: 10 · 2025: 20 · 2024: 18 · 2023: 13 · 2022: 11 · 2021: 21 · 2020: 10 · 2019: 8 · 2018: 15 · 2017: 17 · 2016: 9 · 2015: 7 · 2014: 2
FWCI
1.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Handbook of experimental pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (R01MH076136)
  • National Cancer Institute (U54CA143924)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
Keywords
placebo analgesia, placebo effect, pain processing, dorsal anterior cingulate cortex, thalamus, insula, amygdala, striatum, prefrontal cortex, periaqueductal gray, rostral anterior cingulate cortex, noxious stimulation
MeSH terms
Analgesia, Brain, Humans, Pain, Placebo Effect, Neuroimaging

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