The anatomy of the mesolimbic reward system: a link between personality and the placebo analgesic response
Open accessAbstract
The anticipation of clinical benefit, a crucial component of placebo analgesia, has been suggested to be a special case of reward anticipation. Since reward processing is closely linked to the ventral striatum and the neurotransmitter dopamine, we examined the relationships between brain gray matter, placebo analgesic response, and personality traits associated with dopaminergic neurotransmission. We report that dopamine-related traits predict a substantial portion of the pain relief an individual gains from a sham treatment. Voxel-based morphometry of magnetic resonance images shows that the magnitude of placebo analgesia is related to gray matter density (GMD) in several brain regions, including the ventral striatum, insula, and prefrontal cortex. Similarly, GMD in ventral striatum and prefrontal cortex is related to dopamine-related personality traits. Our findings highlight the relationship between placebo and reward and potentially offer ways of identifying subjects who are likely to show large placebo analgesic responses.
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The experience of pain results from both sensory input and psychological variables such as personality traits and anxiety level.
“The experience of pain results from both sensory input and psychological variables such as personality traits and anxiety level1–5.”
From Boundary effects of expectation in human pain perception (2019) · cites this paper as [5]
The section on dopamine-related personality traits reports that those traits were associated with changes in pain ratings during placebo analgesia, supporting the personality component in that setting. The Placebo analgesic response section reports no correlation between changes in anxiety/calmness and the placebo analgesic response. The paper therefore does not establish the broader claim that anxiety level contributes to pain experience. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe experience of pain is strongly affected by other psychological variables such as optimism, anxiety, suggestibility, and reward responsiveness.
“Our interest in individual differences was motivated by our own and others’ findings that the experience of pain is strongly affected by other psychological variables such as optimism, anxiety, suggestibility, and reward responsiveness1–5.”
From Boundary effects of expectation in human pain perception (2019) · cites this paper as [5]
The Results section (page not supplied) reports that a composite of dopamine-related personality traits was associated with placebo-induced changes in pain, supporting the broad point that psychological differences relate to pain experience. The Discussion (page not supplied) reports a prior finding on suggestibility, but says reward responsiveness alone did not correlate with placebo analgesia. The paper does not establish the claimed effects of optimism or anxiety. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIndividual differences in placebo response were significantly associated with dopamine release under placebo and subsequent activity in reward tasks.
“Individual differences in placebo response were significantly associated with dopamine release under placebo and subsequent activity in reward tasks (Schweinhardt et al., 2009).”
From Distinct neural representations of placebo and nocebo effects (2015) · cites this paper as Schweinhardt et al., 2009
Other traits, like dopamine-related personality traits (harm avoidance and novelty seeking), have been found to predict analgesic placebo responses.
“other traits that have been found to predict analgesic placebo responses30, like dopamine-related personality traits (i.e., harm avoidance and novelty seeking)”
From Changes in perception of treatment efficacy are associated to the magnitude of the nocebo effect and to personality traits (2016) · cites this paper as [30]
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BackgroundDistinct neural representations of placebo and nocebo effects
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“Individual differences in placebo response were significantly associated with dopamine release under placebo and subsequent activity in reward tasks (Schweinhardt et al., 2009).”
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“…Test-Revisited 28 ) and anxiety (State-Trait Anxiety Inventory 29 ), but also other traits that have been found to predict analgesic placebo responses 30 , like dopamine-related personality traits (i.e., harm avoidance and novelty seeking) (Temperament and Character Inventory (TCI 31 ).”
- Authors
- Schweinhardt, P., Seminowicz, D. A., Jaeger, E., Duncan, G. H., & Bushnell, M. C.
- Affiliations
- McGill University (CA)
- Université de Montréal (CA)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-04-15
- Volume
- 29
- Issue
- 15
- Pages
- 4882-4887
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6665321
- OpenAlex
- W2062372003
- Cited by
- 210
- References
- 46
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 6 · 2023: 10 · 2022: 7 · 2021: 13 · 2020: 16 · 2019: 7 · 2018: 15 · 2017: 14 · 2016: 8 · 2015: 17 · 2014: 25 · 2013: 18 · 2012: 15
- FWCI
- 6.47
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- placebo analgesia, mesolimbic reward system, reward anticipation, ventral striatum, gray matter density, prefrontal cortex, insula, sham treatment, analgesia
- MeSH terms
- Administration, Topical, Adolescent, Adult, Analgesics, Humans, Limbic System, Male, Mesencephalon, Nerve Net, Pain Measurement, Personality, Reward, Placebo Effect, Cross-Over Studies, Young Adult
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