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Spinal p38 MAP kinase is necessary for NMDA-induced spinal PGE2 release and thermal hyperalgesia

Svensson, Camilla I.1 2 CA; Hua, Xiao-Ying2; Protter, Andrew A.3; Powell, Henry C.1 2; Yaksh, Tony L.2


Based on previous work, we hypothesized that activation of spinal NMDA-receptor initiates activation of the p38 mitogen-activated protein kinase (p38 MAPK) pathway, leading to spinal release of prostaglandins and hyperalgesia. Accordingly, we examined the effect of intrathecal SD-282, a selective p38 MAPK inhibitor, on NMDA-induced release of prostaglandin E2 (PGE2) and thermal hyperalgesia. Inhibition of spinal p38 MAPK attenuated both NMDA-evoked release of PGE2 and thermal hyperalgesia. NMDA injection led to increased phospho-p38 MAPK immunoreactivity in superficial (I–II) dorsal laminae. Co-labeling studies revealed co-localization of activated p38 MAPK predominantly with microglia but also with a small subpopulation of neurons. Taken together these data suggest a role for p38 MAPK in NMDA-induced PGE2 release and hyperalgesia, and that microglia is involved in spinal nociceptive processing.

1Department of Pathology

2Department of Anesthesiology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0612

3Scios Inc., Sunnyvale, CA, USA

Received 10 December 2002; accepted 26 February 2003

CACorresponding Author:

© 2003 Lippincott Williams & Wilkins, Inc.