Placebo analgesia: findings from brain imaging studies and emerging hypotheses
Abstract
Placebo analgesia is one of the most robust and best-studied placebo effects. With the help of brain imaging tools, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), our understanding of the brain's role in placebo analgesia has been greatly expanded. Previous studies suggest that multiple mechanisms may underlie the phenomenon of placebo analgesia. This review posits a theoretical framework for interpreting the results of the neuroimaging literature of placebo analgesia. According to this framework, placebo treatment may exert an analgesic effect on at least three stages of pain processing, by 1) influencing pre-stimulus expectation of pain relief, 2) modifying pain perception, and 3) distorting post-stimulus pain rating. Importantly, change in one such stage may hasten change in another, and furthermore, contribution from any or all of the three stages may vary by circumstance, or between individuals. The literature suggests that multiple brain regions, including the anterior cingulate cortex, anterior insula, prefrontal cortex and periaqueductal grey, play a pivotal role in these processes.
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An inert treatment could function through three interrelated processes to produce placebo and nocebo effects.
“Theoretically, an inert treatment could function through three interrelated processes to produce placebo and nocebo effects (Amanzio et al., 2013; Kong et al., 2007).”
From Distinct neural representations of placebo and nocebo effects (2015) · cites this paper as Kong et al., 2007
In the third stage, after the pain stimulus ends and subjects evaluate pain intensity, memory of previous experience or context may subconsciously distort decision-making.
“Finally, in the third stage, when the pain stimulus has ended and when subjects are required to evaluate the pain intensity, memory of previous experience/context may subconsciously distort the decision-making process, a construct we have described as selective distortion of pain intensity evaluation (Kong et al., 2007).”
From Distinct neural representations of placebo and nocebo effects (2015) · cites this paper as Kong et al., 2007
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Belief or Need? Accounting for individual variations in the neurochemistry of the placebo effect
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Activation of the Opioidergic Descending Pain Control System Underlies Placebo Analgesia
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Placebo Analgesia: A Predictive Coding Perspective
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A functional magnetic resonance imaging study on the neural mechanisms of hyperalgesic nocebo effect
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Neural bases of conditioned placebo analgesia
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“[5,19,38]).”
Mental Health Benefits of Strength Training in Adults
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Distinct neural representations of placebo and nocebo effects
Freeman, S., Yu, R., Egorova, N., Chen, X., Kirsch, I., Claggett, B., Kaptchuk, T. J., Gollub, R. L., & Kong, J. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.03.015 · Cited by 116 · see citing works
“We also found a correlation between the placebo effect and activity in the dmPFC, which is a part of the pain matrix, implicated emotion regulation (Kong et al., 2007) and pain modulation (Fields, 2000; Kong et al., 2007, 2010b, 2013).”
BackgroundMethodResultInfluentialSelf-citationMechanisms of the placebo response
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Self-citationHypnotic susceptibility modulates brain activity related to experimental placebo analgesia
Huber, A., Lui, F., & Porro, C. A. (2013) · Pain · doi:10.1016/j.pain.2013.03.031 · Cited by 53 · see citing works
- Authors
- Kong, J., Kaptchuk, T. J., Polich, G., Kirsch, I., & Gollub, R. L.
- Affiliations
- Harvard University (US)
- Venue
- Reviews in the Neurosciences
- Publisher
- Walter de Gruyter GmbH
- Published
- 2007-01
- Volume
- 18
- Issue
- 3-4
- Pages
- 173-90
- ISSN
- 0334-1763 (ISSN-L)
- 2191-0200
- OpenAlex
- W1997667062
- Cited by
- 97
- References
- 119
- Citations by year
- 2025: 3 · 2024: 8 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 5 · 2017: 1 · 2016: 2 · 2015: 7 · 2014: 6 · 2013: 7 · 2012: 5
- FWCI
- 0.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Reviews in the Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Center for Complementary and Integrative Health (K01AT003883)
- 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, pain anticipation, pain perception, pain scores, anterior cingulate cortex, anterior insula, prefrontal cortex, periaqueductal gray
- MeSH terms
- Analgesia, Animals, Brain, Humans, Magnetic Resonance Imaging, Neural Pathways, Pain, Perception, Placebo Effect, Pain Threshold, Positron-Emission Tomography, Pain Management
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