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
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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“chronic pain is also associated with elevated levels of inflammation and that such inflammation drives hyperalgesia, or increased sensitivity to pain”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Watkins & Maier, 2000
In the citing paper
“afferent nerve activation in response to inflammatory signaling in the periphery induces the release of proinflammatory cytokines in the brain”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Watkins & Maier, 2000
In the citing paper
“The influence on the brain of stimuli such as cytokines and vagal signaling has been well characterized in animal models of inflammation, and the constellation of psychological symptoms associated with inflammation (fatigue, social withdrawal and loss of appetite) has been labeled the sickness behavior syndrome.72”
From Principles and clinical implications of the brain-gut-enteric microbiota axis (2009) · cites this paper as [72]
In the citing paper
“The influence on the brain of stimuli such as cytokines and vagal signaling has been well characterized in animal models of inflammation, and the constellation of psychological symptoms associated with inflammation (fatigue, social withdrawal and loss of appetite) has been labeled the sickness behavior syndrome.72”
From Principles and clinical implications of the brain-gut-enteric microbiota axis (2009) · cites this paper as [72]
Citations
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Cited by
Sorted by citations
Slavich, G. M., & Irwin, M. R. (2014) · Psychological Bulletin · doi:10.1037/a0035302 · Cited by 2,206
Gut feelings: the emerging biology of gut-brain communication
Mayer, E. A. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3071 · Cited by 1,726
Twenty years of research on cytokine-induced sickness behavior
Dantzer, R., & Kelley, K. W. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2006.09.006 · Cited by 1,420
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Emotions, morbidity, and mortality: new perspectives from psychoneuroimmunology.
Kiecolt-Glaser, J. K., McGuire, L., Robles, T. F., & Glaser, R. (2002) · Annual Review of Psychology · doi:10.1146/annurev.psych.53.100901.135217 · Cited by 1,176
Metadata
- Authors
- Watkins, L. R., & Maier, S. F.
- Affiliations
- University of Colorado Boulder (US)
- 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
- 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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