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

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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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Crossref · 10.1146/annurev.psych.51.1.29

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Authors: Watkins, L. R., & Maier, S. F.
Affiliations: University of Colorado Boulder (US)
ORCID: Watkins, L. R.
Maier, S. F.
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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The Pain of Being Sick: Implications of Immune-to-Brain Communication for Understanding Pain

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