The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Millan, M. J. (2002) · Progress in Neurobiology · doi:10.1016/s0301-0082(02)00009-6 · Cited by 3,035
Endogenous Pain Control Systems: Brainstem Spinal Pathways and Endorphin Circuitry
Basbaum, A. I., & Fields, H. L. (1984) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.07.030184.001521 · Cited by 2,687
Using confidence intervals in within-subject designs
Loftus, G. R., & Masson, M. E. J. (1994) · Psychonomic Bulletin & Review · doi:10.3758/bf03210951 · Cited by 2,433
Placebo-Induced Changes in fMRI in the Anticipation and Experience of Pain
Wager, T. D., Rilling, J. K., Smith, E. E., Sokolik, A., Casey, K. L., Davidson, R. J., Kosslyn, S. M., Rose, R. M., & Cohen, J. D. (2004) · Science · doi:10.1126/science.1093065 · Cited by 1,992
THE MECHANISM OF PLACEBO ANALGESIA
Levine, J., Gordon, N., & Fields, H. (1978) · The Lancet · doi:10.1016/s0140-6736(78)92762-9 · Cited by 1,094
State-dependent opioid control of pain
Fields, H. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1431 · Cited by 946 · cited 4×
“, 2009a), and given its bidirectional control of pain modulation (Fields, 2004), it is probably also engaged in nocebo hyperalgesia.”
BackgroundInfluentialAmanzio, M., & Benedetti, F. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-01-00484.1999 · Cited by 899
Activation of the Opioidergic Descending Pain Control System Underlies Placebo Analgesia
Eippert, F., Bingel, U., Schoell, E. D., Yacubian, J., Klinger, R., Lorenz, J., & Büchel, C. (2009) · Neuron · doi:10.1016/j.neuron.2009.07.014 · Cited by 839
Self-citationBingel, U., Wanigasekera, V., Wiech, K., Ni Mhuircheartaigh, R., Lee, M. C., Ploner, M., & Tracey, I. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3001244 · Cited by 810
Light, A. R., & Perl, E. R. (1979) · The Journal of Comparative Neurology · doi:10.1002/cne.901860203 · Cited by 797
The subjective experience of pain: where expectations become reality
Koyama, T., McHaffie, J. G., Laurienti, P. J., & Coghill, R. C. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408576102 · Cited by 747
Valet, M., Sprenger, T., Boecker, H., Willoch, F., Rummeny, E., Conrad, B., Erhard, P., & Tolle, T. R. (2004) · Pain · doi:10.1016/j.pain.2004.02.033 · Cited by 708
Placebo and Nocebo Effects Are Defined by Opposite Opioid and Dopaminergic Responses
Scott, D. J., Stohler, C. S., Egnatuk, C. M., Wang, H., Koeppe, R. A., & Zubieta, J.-K. (2008) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2007.34 · Cited by 637
New Insights into the Placebo and Nocebo Responses
Enck, P., Benedetti, F., & Schedlowski, M. (2008) · Neuron · doi:10.1016/j.neuron.2008.06.030 · Cited by 547
Supraspinal contributions to hyperalgesia
Urban, M. O., & Gebhart, G. F. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.14.7687 · Cited by 518
Direct evidence for spinal cord involvement in placebo analgesia
Eippert, F., Finsterbusch, J., Bingel, U., & Büchel, C. (2009) · Science · doi:10.1126/science.1180142 · Cited by 512
Self-citationThe role of learning in nocebo and placebo effects
Colloca, L., Sigaudo, M., & Benedetti, F. (2008) · Pain · doi:10.1016/j.pain.2008.02.006 · Cited by 411
Mechanisms of Placebo and Placebo-Related Effects Across Diseases and Treatments
Benedetti, F. (2007) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.48.113006.094711 · Cited by 398
Brain mediators of predictive cue effects on perceived pain
Atlas, L. Y., Bolger, N., Lindquist, M. A., & Wager, T. D. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.0057-10.2010 · Cited by 389
The role of conditioning and verbal expectancy in the placebo response
Voudouris, N. J., Peck, C. L., & Coleman, G. (1990) · Pain · doi:10.1016/0304-3959(90)90057-k · Cited by 369
Descending analgesia – When the spine echoes what the brain expects
Goffaux, P., Redmond, W. J., Rainville, P., & Marchand, S. (2007) · Pain · doi:10.1016/j.pain.2006.11.011 · Cited by 342
Visualization of Group Inference Data in Functional Neuroimaging
Gläscher, J. P. (2009) · Neuroinformatics · doi:10.1007/s12021-008-9042-x · Cited by 306
How the number of learning trials affects placebo and nocebo responses
Colloca, L., Petrovic, P., Wager, T. D., Ingvar, M., & Benedetti, F. (2010) · Pain · doi:10.1016/j.pain.2010.08.007 · Cited by 300
A functional magnetic resonance imaging study on the neural mechanisms of hyperalgesic nocebo effect
Kong, J., Gollub, R. L., Polich, G., Kirsch, I., LaViolette, P., Vangel, M., Rosen, B., & Kaptchuk, T. J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.2944-08.2008 · Cited by 263 · cited 2×
“Nocebo-induced hyperalgesia increases pain along with activity in cortical painprocessing areas (Kong et al., 2008; Rodriguez-Raecke et al., 2010).”
BackgroundPerformance-dependent inhibition of pain by an executive working memory task
Buhle, J., & Wager, T. D. (2010) · Pain · doi:10.1016/j.pain.2009.10.027 · Cited by 249
Physiological noise modelling for spinal functional magnetic resonance imaging studies
Brooks, J. C. W., Beckmann, C. F., Miller, K. L., Wise, R. G., Porro, C. A., Tracey, I., & Jenkinson, M. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.09.018 · Cited by 243
Estimation of Effect Size From a Series of Experiments Involving Paired Comparisons
Gibbons, R. D., Hedeker, D., & Davis, J. M. (1993) · Journal of Educational Statistics · doi:10.3102/10769986018003271 · Cited by 230
Kovelowski, C. J., Ossipov, M. H., Sun, H., Lai, J., Malan, T. P., & Porreca, F. (2000) · Pain · doi:10.1016/s0304-3959(00)00290-6 · Cited by 211
Attention modulates spinal cord responses to pain
Sprenger, C., Eippert, F., Finsterbusch, J., Bingel, U., Rose, M., & Büchel, C. (2012) · Current Biology · doi:10.1016/j.cub.2012.04.006 · Cited by 207
Self-citationConditioned response models of placebo phenomena: further support
Voudouris, N. J., Peck, C. L., & Coleman, G. J. (1989) · Pain · doi:10.1016/0304-3959(89)90080-8 · Cited by 200
Mechanisms of Placebo Pain Reduction: An Empirical Investigation
Montgomery, G. H., & Kirsch, I. (1996) · Psychological Science · doi:10.1111/j.1467-9280.1996.tb00352.x · Cited by 156
Nociceptive facilitating neurons in the rostral ventromedial medulla
Neubert, M. J., Kincaid, W., & Heinricher, M. M. (2004) · Pain · doi:10.1016/j.pain.2004.03.017 · Cited by 141
Lorenz, J., Hauck, M., Paur, R. C., Nakamura, Y., Zimmermann, R., Bromm, B., & Engel, A. K. (2005) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2005.03.010 · Cited by 138
Wang, X., Zhang, J., Eberhart, D. E., Urban, R., Meda, K., Solórzano, C., Yamanaka, H., Rice, D. S., & Basbaum, A. I. (2013) · Neuron · doi:10.1016/j.neuron.2013.03.001 · Cited by 129
Franz, V. H., & Loftus, G. R. (2012) · Psychonomic Bulletin & Review · doi:10.3758/s13423-012-0230-1 · Cited by 118
Pain sensitivity and vasopressin analgesia are mediated by a gene-sex-environment interaction
Mogil, J. S., Sorge, R. E., LaCroix‐Fralish, M. L., Smith, S. B., Fortin, A., Sotocinal, S. G., Ritchie, J., Austin, J., Schorscher-Petcu, A., Melmed, K. R., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2941 · Cited by 115
Consistency of the placebo effect
Whalley, B., Hyland, M. E., & Kirsch, I. (2008) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2007.11.007 · Cited by 107
Quantitative proton magnetic resonance spectroscopy of the cervical spinal cord
Cooke, F. J., Blamire, A. M., Manners, D. N., Styles, P., & Rajagopalan, B. (2004) · Magnetic Resonance in Medicine · doi:10.1002/mrm.20084 · Cited by 95
Rodriguez‐Raecke, R., Doganci, B., Breimhorst, M., Stankewitz, A., Büchel, C., Birklein, F., & May, A. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2197-10.2010 · Cited by 89
Self-citationAssessment of physiological noise modelling methods for functional imaging of the spinal cord
Kong, Y., Jenkinson, M., Andersson, J., Tracey, I., & Brooks, J. C. W. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.11.077 · Cited by 84
Single, slice-specific z-shim gradient pulses improve T2*-weighted imaging of the spinal cord
Finsterbusch, J., Eippert, F., & Büchel, C. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.09.038 · Cited by 80
Self-citationSummers, P. E., Ferraro, D., Duzzi, D., Lui, F., Iannetti, G. D., & Porro, C. A. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.01.043 · Cited by 65
Characterization of cardiac-related noise in fMRI of the cervical spinal cord
Piché, M., Cohen‐Adad, J., Nejad, M. K., Perlbarg, V., Xie, G., Beaudoin, G., Benali, H., & Rainville, P. (2008) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2008.07.019 · Cited by 61
Finsterbusch, J., Sprenger, C., & Büchel, C. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2013.04.021 · Cited by 59
Self-citationCognitive Reversal of Expected Nitrous Oxide Analgesia for Acute Pain
Dworkin, S. F., Chen, A. C. N., LeResche, L., & Clark, D. W. (1983) · Anesthesia & Analgesia · doi:10.1213/00000539-198312000-00005 · Cited by 59
Cognitive Reversal of Expected Nitrous Oxide Analgesia for Acute Pain
Dworkin, S. F., Chen, A. C. N., LeResche, L., & Clark, D. W. (1984) · Survey of Anesthesiology · doi:10.1097/00132586-198408000-00072 · Cited by 57
Stimulus Site and Modality Dependence of Functional Activity within the Human Spinal Cord
Brooks, J. C. W., Kong, Y., Lee, M., Warnaby, C. E., Wanigasekera, V., Jenkinson, M., & Tracey, I. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.2543-11.2012 · Cited by 56
Cahill, C. M., & Stroman, P. W. (2011) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2010.10.007 · Cited by 55
Marshall, T. M., Herman, D. S., Largent-Milnes, T., Badghisi, H., Zuber, K., Holt, S. C., Lai, J., Porreca, F., & Vanderah, T. (2011) · Pain · doi:10.1016/j.pain.2011.09.021 · Cited by 46
Placebo analgesia and nocebo hyperalgesia – Two sides of the same coin?
Petrović, P. (2008) · Pain · doi:10.1016/j.pain.2008.03.004 · Cited by 34
Sotgiu, M. L., Brambilla, M., Valente, M., & Biella, G. E. M. (2004) · Somatosensory & Motor Research · doi:10.1080/08990220400012539 · Cited by 20
Seo, Y., Shinar, H., Morita, Y., & Navon, G. (1999) · Magnetic Resonance in Medicine · doi:10.1002/(sici)1522-2594(199909)42:3 · Cited by 19
Glover (2000) · doi:10.1002/1522-2594(200007)44:1
Cited by
Sorted by citations
The neuroscience of placebo effects: connecting context, learning and health
Wager, T. D., & Atlas, L. Y. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3976 · Cited by 844
(2020) · doi:10.1056/nejmra1907805 · Cited by 634
Placebo Analgesia: A Predictive Coding Perspective
Büchel, C., Geuter, S., Sprenger, C., & Eippert, F. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.042 · Cited by 505
Self-citationPain vulnerability: a neurobiological perspective
Denk, F., McMahon, S. B., & Tracey, I. (2014) · Nature Neuroscience · doi:10.1038/nn.3628 · Cited by 363
Schedlowski, M., Enck, P., Rief, W., & Bingel, U. (2015) · Pharmacological Reviews · doi:10.1124/pr.114.009423 · Cited by 323
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
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
