Interleukin-1β-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity

Tarek A. Samad, Kimberly A. Moore, Adam Sapirstein, Sara Billet, Andrew Allchorne, Stephen Poole, Joseph V. Bonventre and Clifford J. Woolf ()
Additional contact information
Tarek A. Samad: Neural Plasticity Research Group
Kimberly A. Moore: Neural Plasticity Research Group
Adam Sapirstein: Massachusetts General Hospital and Harvard Medical School
Sara Billet: Neural Plasticity Research Group
Andrew Allchorne: University College London
Stephen Poole: National Institute for Biological Standards and Control
Joseph V. Bonventre: Neural Plasticity Research Group
Clifford J. Woolf: Neural Plasticity Research Group

Nature, 2001, vol. 410, issue 6827, 471-475

Abstract: Abstract Inflammation causes the induction of cyclooxygenase-2 (Cox-2)1, leading to the release of prostanoids, which sensitize peripheral nociceptor terminals and produce localized pain hypersensitivity2. Peripheral inflammation also generates pain hypersensitivity in neighbouring uninjured tissue (secondary hyperalgesia), because of increased neuronal excitability in the spinal cord (central sensitization)3, and a syndrome comprising diffuse muscle and joint pain, fever, lethargy and anorexia4. Here we show that Cox-2 may be involved in these central nervous system (CNS) responses, by finding a widespread induction of Cox-2 expression in spinal cord neurons and in other regions of the CNS, elevating prostaglandin E2 (PGE2) levels in the cerebrospinal fluid. The major inducer of central Cox-2 upregulation is interleukin-1β in the CNS, and as basal phospholipase A2 activity in the CNS does not change with peripheral inflammation, Cox-2 levels must regulate central prostanoid production. Intraspinal administration of an interleukin-converting enzyme or Cox-2 inhibitor decreases inflammation-induced central PGE2 levels and mechanical hyperalgesia. Thus, preventing central prostanoid production by inhibiting the interleukin-1β-mediated induction of Cox-2 in neurons or by inhibiting central Cox-2 activity reduces centrally generated inflammatory pain hypersensitivity.

Date: 2001
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/35068566 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:410:y:2001:i:6827:d:10.1038_35068566

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/35068566

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().