The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
A Functional Magnetic Resonance Imaging Study on the Neural Mechanisms of Hyperalgesic Nocebo Effect
Open accessAbstract
Previous studies suggest that nocebo effects, sometimes termed “negative placebo effects,” can contribute appreciably to a variety of medical symptoms and adverse events in clinical trials and medical care. In this study, using a within-subject design, we combined functional magnetic resonance imaging (fMRI) and an expectation/conditioning manipulation model to investigate the neural substrates of nocebo hyperalgesia using heat pain on the right forearm. Thirteen subjects completed the study. Results showed that, after administering inert treatment, subjective pain intensity ratings increased significantly more on nocebo regions compared with the control regions in which no expectancy/conditioning manipulation was performed. fMRI analysis of hyperalgesic nocebo responses to identical calibrated noxious stimuli showed signal increases in brain regions including bilateral dorsal anterior cingulate cortex (ACC), insula, superior temporal gyrus; left frontal and parietal operculum, medial frontal gyrus, orbital prefrontal cortex, superior parietal lobule, and hippocampus; right claustrum/putamen, lateral prefrontal gyrus, and middle temporal gyrus. Functional connectivity analysis of spontaneous resting-state fMRI data from the same cohort of subjects showed a correlation between two seed regions (left frontal operculum and hippocampus) and pain network including bilateral insula, operculum, ACC, and left S1/M1. In conclusion, we found evidence that nocebo hyperalgesia may be predominantly produced through an affective–cognitive pain pathway (medial pain system), and the left hippocampus may play an important role in this process.
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“Previous neuroimaging studies have also shown that nocebo effects are mediated by the hippocampus and regions involved in anticipatory anxiety processing (Bingel et al., 2011; Kong et al., 2008; Ploghaus et al., 2001).”
From Distinct neural representations of placebo and nocebo effects (2015) · cites this paper as Kong et al., 2008
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Citations
Cites
Functional connectivity in the motor cortex of resting human brain using echo‐planar mri
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“In an early study, Biswal et al. (1995) found that, while subjects were at rest, spontaneous fMRI blood oxygen leveldependent signal fluctuations observed in left sensory motor areas showed a high degree of temporal correlation with right sensory motor-related brain areas and medial motor areas.”
The human brain is intrinsically organized into dynamic, anticorrelated functional networks
Fox, M. D., Snyder, A. Z., Vincent, J. L., Corbetta, M., Van Essen, D. C., & Raichle, M. E. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504136102 · Cited by 8,553 · cited 1×
“Methods for functional connectivity analysis were adopted from previous studies (Fox et al., 2005; AndrewsHanna et al., 2007; Vincent et al., 2007).”
Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging
Fox, M. D., & Raichle, M. E. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2201 · Cited by 6,700 · cited 4×
“At the very beginning of fMRI scanning session, we also collected a 6 min spontaneous fMRI data set to investigate functional connectivity (Raichle and Mintun, 2006; Buckner and Vincent, 2007; Fox and Raichle, 2007) among the brain regions observed to be activated in the subsequent analysis of the nocebo scans.”
InfluentialHuman brain mechanisms of pain perception and regulation in health and disease
Apkarian, A. V., Bushnell, M. C., Treede, R., & Zubieta, J. (2005) · European Journal of Pain · doi:10.1016/j.ejpain.2004.11.001 · Cited by 3,126 · cited 2×
“…Neuroscience 0270-6474/08/2813354-09$15.00/0 Previous studies have suggested that the central pain matrix consists of approximately two parallel subsystems, the lateral (sensory– discriminatory) and medial (affective– cognitive evaluation) system (Apkarian et al., 2005; Tracey and Mantyh, 2007).”
InfluentialPain Affect Encoded in Human Anterior Cingulate But Not Somatosensory Cortex
Rainville, P., Duncan, G. H., Price, D. D., Carrier, B., & Bushnell, M. C. (1997) · Science · doi:10.1126/science.277.5328.968 · Cited by 2,629 · cited 1×
“In this experiment, we found a significant fMRI signal increase to pain in bilateral ACC, a key region involved in processing the affective components of pain (Rainville et al., 1997; Price, 2000; Rainville, 2002).”
Functional imaging of brain responses to pain. A review and meta-analysis (2000)
Peyron, R., Laurent, B., & García-Larrea, L. (2000) · Neurophysiologie Clinique/Clinical Neurophysiology · doi:10.1016/s0987-7053(00)00227-6 · Cited by 2,171 · cited 1×
“Previous studies implicate operculum/insula as the most reliable region in brain imaging studies on pain (Peyron et al., 2000) and report its direct association with S1, SII, prefrontal areas, superior temporal gyrus, amygdaloid, and perirhinal cortex, which is an important source of hippocampal…”
Psychological and neural mechanisms of the affective dimension of pain
Price, D. D. (2000) · Science · doi:10.1126/science.288.5472.1769 · Cited by 2,092 · cited 3×
“In this experiment, we found a significant fMRI signal increase to pain in bilateral ACC, a key region involved in processing the affective components of pain (Rainville et al., 1997; Price, 2000; Rainville, 2002).”
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 · cited 7×
“…2001); (3) has not been reported in the substantial placebo analgesia neuroimaging literature base (Petrovic et al., 2002; Lieberman et al., 2004; Wager et al., 2004, 2007); Zubieta et al., 2005; Bingel et al., 2006; Kong et al., 2006a; Craggs et al., 2007; Price et al., 2007; Scott et al.,…”
MethodInfluentialThe Cerebral Signature for Pain Perception and Its Modulation
Tracey, I., & Mantyh, P. W. (2007) · Neuron · doi:10.1016/j.neuron.2007.07.012 · Cited by 1,843 · cited 2×
“Previous studies have suggested that the central pain matrix consists of approximately two parallel subsystems, the lateral (sensory– discriminatory) and medial (affective– cognitive evaluation) system (Apkarian et al., 2005; Tracey and Mantyh, 2007).”
InfluentialPain and emotion interactions in subregions of the cingulate gyrus
Vogt, B. A. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1704 · Cited by 1,810 · cited 2×
“The medial system projects through the medial thalamic nuclei to the cortex and includes the anterior cingulate cortex (ACC), insula, and prefrontal cortices (Price, 2000; Rainville, 2002; Vogt, 2005).”
Cited by
Sorted by citations
Biological, clinical, and ethical advances of placebo effects
Finniss, D. G., Kaptchuk, T. J., Miller, F. G., & Benedetti, F. (2010) · The Lancet · doi:10.1016/s0140-6736(09)61706-2 · Cited by 1,309
“71”
Self-citationBernhardt, B. C., & Singer, T. (2012) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-062111-150536 · Cited by 952
“ACC and insula responses vary not simply as a function of noxious input but rather as a function of subjectively felt pain intensity (Kong et al. 2008).”
BackgroundBingel, 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
“Activity in medial frontal areas and hippocampus has also been observed in a recent study on the nocebo hyperalgesic effects during sham acupuncture (29).”
The influence of negative emotions on pain: Behavioral effects and neural mechanisms
Wiech, K., & Tracey, I. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.05.059 · Cited by 614
“In a recent fMRI study activation in the anterior insula was not simply driven by the noxious input but was more pronounced when participants were instructed to rate their subjective intensity of pain (Kong et al., 2008).”
Getting the pain you expect: mechanisms of placebo, nocebo and reappraisal effects in humans
Tracey, I. (2010) · Nature Medicine · doi:10.1038/nm.2229 · Cited by 553
“A recent neuroimaging study has shown that nocebo effects are mediated by the hippocampus and regions involved with anticipatory anxiety and, as such, are distinct from placebo effects at a neural leve”
Background
Metadata
- Authors
- Kong, J., Gollub, R. L., Polich, G., Kirsch, I., LaViolette, P., Vangel, M., Rosen, B., & Kaptchuk, T. J.
- Affiliations
- Harvard University (US)
- Massachusetts General Hospital (US)
- University of Hull (GB)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-12-03
- Volume
- 28
- Issue
- 49
- Pages
- 13354-13362
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2649754
- OpenAlex
- W2143071887
- Cited by
- 263
- References
- 59
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 15 · 2023: 5 · 2022: 15 · 2021: 16 · 2020: 16 · 2019: 16 · 2018: 11 · 2017: 11 · 2016: 14 · 2015: 19 · 2014: 23 · 2013: 26 · 2012: 19
- FWCI
- 7.48
- 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
- National Institutes of Health (RR14075)
- National Center for Complementary and Alternative Medicine
- National Center for Research Resources (RR 14075, M01RR001066, P41RR014075)
- National Center for Complementary and Integrative Health (K24AT004095, R21AT001922, R21AT000949, P01AT002048, K01AT003883)
- 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, hyperalgesia, thermal pain, pain anticipation, dorsal anterior cingulate cortex, insula, hippocampus, frontal operculum, resting-state functional connectivity, pain network
- MeSH terms
- Adult, Brain, Brain Mapping, Cognition, Conditioning, Psychological, Female, Hippocampus, Humans, Hyperalgesia, Illusions, Functional Laterality, Magnetic Resonance Imaging, Male, Nerve Net, Neuropsychological Tests, Pain, Pain Measurement, Physical Stimulation, Placebo Effect, Pain Threshold, Young Adult
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