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 E 2 (PGE 2 ). 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 PGE 2 in the cerebrospinal fluid. Blockade of the sciatic nerve did not prevent the increases in Cox-2 or PGE 2 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 PGE 2 . 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]