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Neural circuitry engaged by prostaglandins during the sickness syndrome

Abstract

During illnesses caused by infectious disease or other sources of inflammation, a suite of brain-mediated responses called the sickness syndrome occurs, which includes fever, anorexia, sleepiness, hyperalgesia and elevated corticosteroid secretion. Much of the sickness syndrome is mediated by prostaglandins acting on the brain and can be prevented by nonsteroidal anti-inflammatory drugs, such as aspirin or ibuprofen, that block prostaglandin synthesis. By examining which prostaglandins are produced at which sites and how they interact with the nervous system, researchers have identified specific neural circuits that underlie the sickness syndrome.

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Figure 1: Neuronal pathways causing fever during systemic inflammation in response to PGE2.
Figure 2: Neuronal pathways promoting sleep during systemic inflammation, in response to PGD2.
Figure 3: Neuronal pathways that may cause anorexia during systemic inflammation, in response to PGE2.
Figure 4: Neuronal pathways that may cause hyperalgesia in the first few hours of systemic inflammation in response to PGE2.
Figure 5: Neuronal pathways that may cause elevated secretion of corticosteroids in response to systemic inflammation.

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Acknowledgements

The authors acknowledge support from US Public Health Service grants NS055367 (T.E.S.), HL095491 (C.B.S., T.E.S.), NS072337 (C.B.S.) and NS41233 (A.A.R.).

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Saper, C., Romanovsky, A. & Scammell, T. Neural circuitry engaged by prostaglandins during the sickness syndrome. Nat Neurosci 15, 1088–1095 (2012). https://doi.org/10.1038/nn.3159

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