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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Biological basis of the behavior of sick animals
Hart, B. L. (1988) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(88)80004-6 · Cited by 2,223
Treatment of Rheumatoid Arthritis with a Recombinant Human Tumor Necrosis Factor Receptor (p75)–Fc Fusion Protein
Moreland, L. W., Baumgartner, S. W., Schiff, M. H., Tindall, E. A., Fleischmann, R., Weaver, A. L., Ettlinger, R. E., Cohen, S. B., Koopman, W. J., Mohler, K. M., et al. (1997) · New England Journal of Medicine · doi:10.1056/nejm199707173370301 · Cited by 1,620
Fever: Role of Pyrogens and Cryogens
Kluger, M. J. (1991) · Physiological Reviews · doi:10.1152/physrev.1991.71.1.93 · Cited by 1,220
Cytokines for psychologists: Implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition.
Maier, S. F., & Watkins, L. R. (1998) · Psychological Review · doi:10.1037/0033-295x.105.1.83 · Cited by 1,130
Self-citation
Interleukin-1 regulates synthesis of nerve growth factor in non-neuronal cells of rat sciatic nerve
Lindholm, D., Heumann, R., Meyer, M., & Thoenen, H. (1987) · Nature · doi:10.1038/330658a0 · Cited by 994
The pivotal role of tumour necrosis factor α in the development of inflammatory hyperalgesia
Cunha, F. Q., Poole, S., Lorenzetti, B. B., & Ferreira, S. H. (1992) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1992.tb14503.x · Cited by 792
Nerve growth factor contributes to the generation of inflammatory sensory hypersensitivity
Woolf, C. J., Safieh‐Garabedian, B., Ma, Q., Crilly, P. J., & Winter, J. (1994) · Neuroscience · doi:10.1016/0306-4522(94)90366-2 · Cited by 695
Cytokines, nerve growth factor and inflammatory hyperalgesia: the contribution of tumour necrosis factor α
Woolf, C. J., Allchorne, A. J., Safieh‐Garabedian, B., & Poole, S. (1997) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0701148 · Cited by 675
Immune activation: the role of pro-inflammatory cytokines in inflammation, illness responses and pathological pain states
Watkins, L. R., Maier, S. F., & Goehler, L. E. (1995) · Pain · doi:10.1016/0304-3959(95)00186-7 · Cited by 659
Self-citation
Interleukin-1β as a potent hyperalgesic agent antagonized by a tripeptide analogue
Ferreira, S. H., Lorenzetti, B. B., Bristow, A. F., & Poole, S. (1988) · Nature · doi:10.1038/334698a0 · Cited by 624

Show all 147 references

Research works printed but not linked: 20

1995, J. Neurochem., 65, 850
1997, Soc. Neurosci. Abstr., 23, 166
1994, Soc. Neurosci. Abstr., 23, 166
1996, Proc. Soc. Neurosci., 22, 865
Fu K, Light AR, Maixner W. 1998. Long-lasting inflammation and hyperalgesia evoked by subcutaneous formalin injection: associated with spinal microglial activation.Proc. Soc. Neurosci.24:152.2
Hammack S, Milligan E, Nguyen K, Hansen M, Martin D, et al. 1999. Sciatic nerve neuritis-induced allodynia and hyperalgesia is blocked by intrathecal application of IL-1 receptor antagonist.Proc. Soc. Neurosci.25: In press
Herzberg U, Frydel BR, Sagen J. 1998. Epineural exposure to HIV viral envelope protein gp120 induces painful peripheral mononeuropathy and spinal gliosis.Proc. Soc. Neurosci.24:547.4
1992, Acta Biol. Hung., 43, 269
1997, Soc. Neurosci. Abstr., 23, 166
Kawatani M, Birder L. 1992. Interleukin-1 facilitates Ca2+ release in acutely dissociated dorsal root ganglion (DRG) cells of rat.Proc. Soc. Neurosci.18:691
Kelly DD, ed. 1986.Annals of the New York Academy of Sciences: Stress Induced Analgesia,Vol. 467. New York: NY Acad. Sci.
1978, Am. Sci., 66, 38
Milligan E, Nguyen K, Hansen M, Martin D, Maier SF, et al. 1999. HIV-1 gp120-enhanced pain responsivity is mediated by activated spinal cord glia.Proc. Soc. Neurosci.25: In press
Milligan ED, Nguyen KT, Hansen M, Maier SF, Watkins LR. 1998. Allodynia and increased dorsal spinal cord interleukin-1beta induced by intrathecal (IT) gp120, an HIV-1 envelope glycoprotein.Proc. Soc. Neurosci.24:155.1
1995, J. Pharmacol. Exp. Ther., 275, 1339
Reeve AJ, Fox A, Walker MJK, Urban L. 1998. Electrophysiological study on the spinal effects of interleukin-1β on the responses of dorsal horn neurones.Proc. Soc. Neurosci.24:155.3
Richardson PM, Murphy PG, Ramer MS, Borthwick L, Bisby MA. 1998. Endogenous interleukin 6 contributes to peripheral neuropathic pain.Proc. Soc. Neurosci.24:548.7
1998, Proc. Soc. Neurosci., 24, 495.4
1995, Proc. Soc. Neurosci., 21, 897
1996, Proc. Soc. Neurosci., 22, 1811

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Siedentopf, F., Tariverdian, N., Rücke, M., Kentenich, H., & Arck, P. (2008) · American Journal of Reproductive Immunology · doi:10.1111/j.1600-0897.2008.00644.x · Cited by 115
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Hernández-Ávalos, I., Mota‐Rojas, D., Mora‐Medina, P., Martı́nez-Burnes, J., Casas-Alvarado, A., Verduzco-Mendoza, A., Lezama-García, K., & Olmos-Hernández, A. S. (2019) · International Journal of Veterinary Science and Medicine · doi:10.1080/23144599.2019.1680044 · Cited by 108
Sex differences in how inflammation affects behavior: what we can learn from experimental inflammatory models in humans
Lasselin, J., Lekander, M., Axelsson, J., & Karshikoff, B. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.06.005 · Cited by 106
Chronic Low Back Pain, Sleep Disturbance, and Interleukin-6
Heffner, K. L., France, C. R., Trost, Z., Ng, H. M., & Pigeon, W. R. (2010) · Clinical Journal of Pain · doi:10.1097/ajp.0b013e3181eef761 · Cited by 108
Changes in immune and glial markers in the CSF of patients with Complex Regional Pain Syndrome
Alexander, G. M., Perreault, M. J., Reichenberger, E. R., & Schwartzman, R. J. (2006) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2006.10.009 · Cited by 105
Why sickness hurts: A central mechanism for pain induced by peripheral inflammation.
Karshikoff, B., Jensen, K., Kosek, E., Kalpouzos, G., Soop, A., Ingvar, M., Höglund, C. O., Lekander, M., & Axelsson, J. (2016) · Brain, behavior, and immunity · doi:10.1016/j.bbi.2016.04.001 · Cited by 93
Inflammatory Response, Reactive Oxygen Species, Programmed (Necrotic-Like And Apoptotic) Cell Death And Cancer
D, J., Roth, J. C., GH, B., JN, W., Kroczak, T. J., & Łoś, M. (2004) · PubMed · doi:10.5281/zenodo.439891 · Cited by 105
Central nervous system recognition of peripheral inflammation: a neural, hormonal collaboration.
Hopkins, S. J. (2007) · Acta bio-medica dell'Ateneo parmense/Acta biomedica · Cited by 102
The state of science in the study of cancer symptom clusters
Xiao, C. (2010) · European Journal of Oncology Nursing · doi:10.1016/j.ejon.2010.05.011 · Cited by 103
Accelerated immunosenescence in rheumatoid arthritis: impact on clinical progression
Bauer, M. E. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00178-w · Cited by 107
Exercise, sleep quality, and mediators of sleep in breast and prostate cancer patients receiving radiation therapy
Sprod, L. K., Palesh, O. G., Janelsins, M. C., Peppone, L. J., Heckler, C. E., Adams, M. J., Morrow, G. R., & Mustian, K. M. (2010) · Community Oncology · doi:10.1016/s1548-5315(11)70427-2 · Cited by 102
Recovery of Endocrine and Inflammatory Mediators Following an Extended Energy Deficit
Henning, P. C., Scofield, D. E., Spiering, B. A., Staab, J. S., Matheny, R. W., Smith, M. A., Bhasin, S., & Nindl, B. C. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-3046 · Cited by 102
Modality and sex differences in pain sensitivity during human endotoxemia
Karshikoff, B., Lekander, M., Soop, A., Lindstedt, F., Ingvar, M., Kosek, E., Höglund, C. O., & Axelsson, J. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.11.014 · Cited by 95
Fibromyalgia pain: do we know the source?
Staud, R. M. (2004) · Current Opinion in Rheumatology · doi:10.1097/00002281-200403000-00016 · Cited by 91
Why Do We Feel Sick When Infected—Can Altruism Play a Role?
Shakhar, K., & Shakhar, G. (2015) · PLoS Biology · doi:10.1371/journal.pbio.1002276 · Cited by 93
Systemic inflammation alters satellite glial cell function and structure. A possible contribution to pain
Blum, E., Procacci, P., Conte, V., & Menachem Hanani, A. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.05.029 · Cited by 93
Postoperative Pain Management and Proinflammatory Cytokines: Animal and Human Studies
Shavit, Y., Fridel, K., & Beilin, B. (2006) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-006-9043-1 · Cited by 90
Pain Catastrophizing and Salivary Cortisol Responses to Laboratory Pain Testing in Temporomandibular Disorder and Healthy Participants
Quartana, P. J., Buenaver, L. F., Edwards, R. R., Klick, B., Haythornthwaite, J. A., & Smith, M. T. (2009) · Journal of Pain · doi:10.1016/j.jpain.2009.07.008 · Cited by 96
Effect of Methylprednisolone on Neuropathic Pain and Spinal Glial Activation in Rats
Takeda, K., Sawamura, S., Sekiyama, H., Tamai, H., & Hanaoka, K. (2004) · Anesthesiology · doi:10.1097/00000542-200405000-00029 · Cited by 90
Armeniacae semen Extract Suppresses Lipopolysaccharide-Induced Expressions of Cycloosygenase-2 and Inducible Nitric Oxide Synthase in Mouse BV2 Microglial Cells
Chang, H., Yang, H.-Y., Lee, T.-H., Shin, M.-C., Lee, M., Shin, M.-S., Kim, C., Kim, O., Hong, S.-P., & Cho, S. (2005) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.28.449 · Cited by 88
Weight, inflammation, cancer-related symptoms and health-related quality of life among breast cancer survivors
Imayama, I., Alfano, C. M., Neuhouser, M. L., George, S. M., Smith, A. W., Baumgartner, R., Baumgartner, K. B., Bernstein, L., Wang, C.-Y., Duggan, C. R., et al. (2013) · Breast Cancer Research and Treatment · doi:10.1007/s10549-013-2594-y · Cited by 90
Impairment of interleukin-1 (IL-1) signaling reduces basal pain sensitivity in mice: genetic, pharmacological and developmental aspects
Wolf, G., Yirmiya, R., Goshen, I., Iverfeldt, K., Holmlund, L., Takeda, K., & Shavit, Y. (2003) · Pain · doi:10.1016/s0304-3959(03)00067-8 · Cited by 88
Depression as an evolutionary strategy for defense against infection
Anders, S. L., Tanaka, M., & Kinney, D. K. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.12.002 · Cited by 87
Psychobiological differences between depression and somatization
Rief, W., Hennings, A., Riemer, S., & Euteneuer, F. (2010) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2010.02.001 · Cited by 85

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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