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Facilitation of Pain in the Human Spinal Cord by Nocebo Treatment
Open accessAbstract
Nocebo hyperalgesia is an increase in subjective pain perception after a patient or subject underwent an inert treatment without any active ingredient. For example, verbal suggestion of increased pain can enhance both pain experience and responses in pain-related cortical brain areas. However, changes in cortical pain responses may be secondary to earlier amplification of incoming pain signals within the spinal cord. To test for a potential early enhancement of pain signals in the dorsal horn of the spinal cord, we combined a nocebo heat pain paradigm with spinal functional magnetic resonance imaging in healthy volunteers. We found that local application of an inert nocebo cream on the forearm increased pain ratings compared with a control cream, and also reduced pain thresholds on the nocebo-treated skin patch. On the neurobiological level, pain stimulation induced a strong activation in the spinal cord at the level of the stimulated dermatomes C5/C6. Comparing pain stimulation under nocebo to a control pain stimulation of the same physical intensity revealed enhanced pain-related activity in the ipsilateral dorsal horn of the spinal cord. Importantly, the activation of the main effect of pain and the nocebo effect spatially overlapped. The current study thus provides direct evidence for a pain-facilitating mechanism in the human spinal cord before cortical processing, which can be activated by cognitive manipulations such as nocebo treatments.
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“If these manipulations affect the reinforcement signal used in calculating prediction errors, it would short-circuit learning by suppressing cue-inconsistent prediction errors.”
From Social information creates self-fulfilling prophecies in judgments of pain, vicarious pain, and cognitive effort (2026) · cites this paper as [46]
Experimental — accuracy not yet measuredIn the citing paper
“Study participants who believed that they were given a stimulant perceived an increase of their tension, despite having taken a muscle relaxant.44”
From Nocebo and pain: an overview of the psychoneurobiological mechanisms (2017) · cites this paper as [44]
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Metadata
- Authors
- Geuter, S., & Büchel, C.
- Affiliations
- University Medical Center Hamburg-Eppendorf (DE)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-08-21
- Volume
- 33
- Issue
- 34
- Pages
- 13784-13790
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6618657
- OpenAlex
- W2076677238
- Cited by
- 152
- References
- 53
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 8 · 2023: 17 · 2022: 8 · 2021: 18 · 2020: 13 · 2019: 6 · 2018: 14 · 2017: 8 · 2016: 10 · 2015: 18 · 2014: 13 · 2013: 1
- FWCI
- 7.68
- 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
- Deutsche Forschungsgemeinschaft (SFB 936)
- 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
- nocebo effect, nocebo hyperalgesia, dorsal horn, pain facilitation, thermal pain, pain perception, pain threshold, placebo effect, cognitive manipulation
- MeSH terms
- Adult, Capsaicin, Female, Humans, Hyperalgesia, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Oxygen, Pain, Pain Measurement, Surveys and Questionnaires, Spinal Cord, Time Factors, Pain Threshold, Young Adult, Pain Perception
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