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Cited by 389Pain Mechanisms and TreatmentsTryptophan and brain disordersNeuroinflammation and Neurodegeneration Mechanisms

The DOI matches its Crossref record; 147 of the 147 references it cites were found in a registry or an index.

The Pain of Being Sick: Implications of Immune-to-Brain Communication for Understanding Pain

Watkins, L. R., Maier, S. F.·2000·Annual Review of Psychology
DOI 10.1146/annurev.psych.51.1.29
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Abstract

This review focuses on the powerful pain facilitatory effects produced by the immune system. Immune cells, activated in response to infection, inflammation, or trauma, release proteins called proinflammatory cytokines. These proinflammatory cytokines signal the central nervous system, thereby creating exaggerated pain as well as an entire constellation of physiological, behavioral, and hormonal changes. These changes are collectively referred to as the sickness response. Release of proinflammatory cytokines by immune cells in the body leads, in turn, to release of proinflammatory cytokines by glia within the brain and spinal cord. Evidence is reviewed supporting the idea that proinflammatory cytokines exert powerful pain facilitatory effects following their release in the body, in the brain, and in the spinal cord. Such exaggerated pain states naturally occur in situations involving infection, inflammation, or trauma of the skin, of peripheral nerves, and of the central nervous system itself. Implications for human pain conditions are discussed.

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Citations

Cites

Research works printed but not linked: 20

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Metadata

Authors
Watkins, L. R., & Maier, S. F.
Affiliations
University of Colorado Boulder (US)
ORCID
Venue
Annual Review of Psychology
Publisher
Annual Reviews
Published
2000-02
Volume
51
Issue
1
Pages
29-57
ISSN
  • 0066-4308 (ISSN-L)
  • 1545-2085
DOI
10.1146/annurev.psych.51.1.29
OpenAlex
W2065514611
Cited by
388
References
147
Citations by year
2026: 4 · 2025: 6 · 2024: 6 · 2023: 8 · 2022: 5 · 2021: 8 · 2020: 12 · 2019: 14 · 2018: 11 · 2017: 5 · 2016: 10 · 2015: 16 · 2014: 10 · 2013: 17 · 2012: 19
FWCI
2.27
Type
journal article
Language
en
Open access
closed
Locations
  • Annual Review of Psychology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01mh045045-12)
  • National Institute of Mental Health (MH 01558, MH 50479, MH-45045)
Topics
  • Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
inflammatory cytokines, sickness behavior, pain facilitation, neuroinflammation, glial activation, central sensitization, infection, inflammation, trauma (physical injury), peripheral nerve injury, central nervous system injury
MeSH terms
Analgesia, Central Nervous System, Humans, Hyperalgesia, Immune System, Immunity, Inhibition, Psychological, Nerve Net, Pain, Cytokines

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