Sci. STKE, 27 March 2001
Pain Perception Cox-2 in the CNS
Two groups (Ek et al. and Samad et al.) report that the central nervous system may be able to respond to peripheral local inflammation with increased production of prostaglandin pain mediators within the central nervous system, such as prostaglandin E2 (PGE2). Ek et al. focused on the changes in the expression of prostaglandin E synthase and cyclooxygenase in the cerebral vasculature and found that the expression of the two genes increases upon intravenous injection of interleukin-1β. Samad et al. found that in animals with inflammation in the hindpaw, there was increased expression of Cox-2 in the spinal cord and specific areas of the brain. This peripheral inflammation was also associated with increased levels of PGE2 in the cerebrospinal fluid. Blockade of the sciatic nerve did not prevent the increases in Cox-2 or PGE2 levels as effectively as administration of an inhibitor of the interleukin-converting enzyme or an antagonist of the interleukin-1 receptor. These data are consistent with the theory that peripheral interleukin-1β produced at the site of inflammation is able to trigger a CNS inflammatory response by increasing the expression of Cox-2 and the production of PGE2. Caveats to these experiments in terms of the amount of interleukin-1β required to produce these results and the potential therapeutic importance of these findings are discussed by Bartfai.
M. Ek, D. Engblom, S. Saha, A. Blomqvist, P.-J. Jakobsson, A. Ericsson-Dahlstrand, Pathway across the blood-brain barrier. Nature 410, 430-431 (2001). [Online Journal]
T. A. Samad, K. A. Moore, A. Sapirstein, S. Billet, A. Allchorne, S. Poole, J. V. Bonventre, C. J. Woolf, Interleukin-1β-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature 410, 471-475 (2001). [Online Journal]
T. Bartfai, Telling the brain about pain. Nature 410, 425-427 (2001). [Online Journal]
Citation: Cox-2 in the CNS. Sci. STKE 2001, tw4 (2001).
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