Skip Navigation LinksHome > June 11, 2003 - Volume 14 - Issue 8 > Spinal p38 MAP kinase is necessary for NMDA-induced spinal P...
Somatosensory Systems, Pain

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

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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.

© 2003 Lippincott Williams & Wilkins, Inc.


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