Cited by 822Pain Management and Placebo EffectPain Mechanisms and TreatmentsMemory and Neural Mechanisms

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Exacerbation of Pain by Anxiety Is Associated with Activity in a Hippocampal Network

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Ploghaus, Alexander, Narain, Charvy, Beckmann, Christian F., Clare, Stuart, Bantick, Susanna, Wise, Richard, Matthews, Paul M., Rawlins, J. Nicholas P., Tracey, Irene·2001·The Journal of Neuroscience

DOI 10.1523/jneurosci.21-24-09896.2001PMC PMC6763058

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Abstract

It is common clinical experience that anxiety about pain can exacerbate the pain sensation. Using event-related functional magnetic resonance imaging (FMRI), we compared activation responses to noxious thermal stimulation while perceived pain intensity was manipulated by changes in either physical intensity or induced anxiety. One visual signal, which reliably predicted noxious stimulation of moderate intensity, came to evoke low anxiety about the impending pain. Another visual signal was followed by the same, moderate-intensity stimulation on most of the trials, but occasionally by discriminably stronger noxious stimuli, and came to evoke higher anxiety. We found that the entorhinal cortex of the hippocampal formation responded differentially to identical noxious stimuli, dependent on whether the perceived pain intensity was enhanced by pain-relevant anxiety. During this emotional pain modulation, entorhinal responses predicted activity in closely connected, affective (perigenual cingulate), and intensity coding (mid-insula) areas. Our finding suggests that accurate preparatory information during medical and dental procedures alleviates pain by disengaging the hippocampus. It supports the proposal that during anxiety, the hippocampal formation amplifies aversive events to prime behavioral responses that are adaptive to the worst possible outcome.

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OCHSNER, K., & GROSS, J. (2005) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2005.03.010 · Cited by 4,495
Human 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
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 Neuropsychology of Anxiety
Gray, J. A., & McNaughton, N. (2003) · doi:10.1093/acprof:oso/9780198522713.001.0001 · Cited by 1,953
The 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
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Authors: Ploghaus, A., Narain, C., Beckmann, C. F., Clare, S., Bantick, S., Wise, R., Matthews, P. M., Rawlins, J. N. P., & Tracey, I.
Affiliations: John Radcliffe Hospital (GB)
University of Oxford (GB)
ORCID: Beckmann, Christian F.
Clare, Stuart
Wise, Richard
Matthews, Paul M.
Tracey, Irene
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2001-12-15
Volume: 21
Issue: 24
Pages: 9896-9903
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.21-24-09896.2001
PMC: PMC6763058
OpenAlex: W1828259239
Cited by: 822
References: 99
Citations by year: 2026: 8 · 2025: 20 · 2024: 27 · 2023: 37 · 2022: 32 · 2021: 42 · 2020: 32 · 2019: 40 · 2018: 32 · 2017: 36 · 2016: 35 · 2015: 47 · 2014: 48 · 2013: 48 · 2012: 35
FWCI: 11.18
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 182 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: pain modulation, hippocampal formation, entorhinal cortex, noxious thermal stimulation, pain intensity, insula, anticipatory anxiety, emotional pain
MeSH terms: Adult, Anxiety, Behavior, Brain Mapping, Conditioning, Classical, Heart Rate, Hot Temperature, Hippocampus, Humans, Hyperalgesia, Magnetic Resonance Imaging, Male, Nerve Net, Pain, Physical Stimulation, Entorhinal Cortex, Parahippocampal Gyrus

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Exacerbation of Pain by Anxiety Is Associated with Activity in a Hippocampal Network

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