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Isolating the Modulatory Effect of Expectation on Pain Transmission: A Functional Magnetic Resonance Imaging Study
Open accessAbstract
We use a novel balanced experimental design to specifically investigate brain mechanisms underlying the modulating effect of expected pain intensity on afferent nociceptive processing and pain perception. We used two visual cues, each conditioned to one of two noxious thermal stimuli [∼48°C (high) or 47°C (low)]. The visual cues were presented just before and during application of the noxious thermal stimulus. Subjects reported significantly higher pain when the noxious stimulus was preceded by the high-intensity visual cue. To control for expectancy effects, for one-half of the runs, the noxious thermal stimuli were accompanied by the cue conditioned to the other stimulus. Comparing functional magnetic resonance imaging blood oxygenation level-dependent activations produced by the high and low thermal stimulus intensities presented with the high-intensity visual cue showed significant activations in nociceptive regions of the thalamus, second somatosensory cortex, and insular cortex. To isolate the effect of expectancy, we compared activations produced by the two visual cues presented with the high-intensity noxious thermal stimulus; this showed significant differences in the ipsilateral caudal anterior cingulate cortex, the head of the caudate, cerebellum, and the contralateral nucleus cuneiformis (nCF). We propose that pain intensity expectancy modulates activations produced by noxious stimuli through a distinct modulatory network that converges with afferent nociceptive input in the nCF.
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“A number of studies have demonstrated an association between endorsing masculinity and a higher pain threshold and tolerance and lower pain ratings 194–198.”
From Evaluating psychosocial contributions to chronic pain outcomes (2018) · cites this paper as [198]
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“Using the Gender Role Expectation of Pain (GREP) questionnaire, Robinson and colleagues found that women were considered more sensitive to pain, less enduring of pain, and more willing to report pain compared to men 194, 198, 200.”
From Evaluating psychosocial contributions to chronic pain outcomes (2018) · cites this paper as [198]
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“A recent study in individuals with irritable bowel syndrome showed that the largest placebo effect occurred in met/met homozygotes.49”
From Nocebo and pain: an overview of the psychoneurobiological mechanisms (2017) · cites this paper as [49]
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Metadata
- Authors
- Keltner, J. R., Furst, A., Fan, C., Redfern, R., Inglis, B., & Fields, H. L.
- Affiliations
- University of California, San Francisco (US)
- University of California, Berkeley (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-04-19
- Volume
- 26
- Issue
- 16
- Pages
- 4437-4443
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6674009
- OpenAlex
- W2160938249
- Cited by
- 346
- References
- 48
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 12 · 2023: 15 · 2022: 12 · 2021: 10 · 2020: 14 · 2019: 22 · 2018: 24 · 2017: 19 · 2016: 14 · 2015: 23 · 2014: 20 · 2013: 16 · 2012: 22
- FWCI
- 8.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- International Anesthesia Research Society
- U.S. Public Health Service (NS 21445)
- National Institute of Neurological Disorders and Stroke (NS21445)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- pain anticipation, pain transmission, nociceptive processing, thermal pain, visual cues, thalamus, secondary somatosensory cortex, insula, caudal anterior cingulate cortex, caudate nucleus, nucleus cuneiformis, pain perception, expectancy effects
- MeSH terms
- Adult, Cues, Hot Temperature, Humans, Magnetic Resonance Imaging, Male, Pain, Pain Measurement, Perception, Photic Stimulation
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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