Spinal p38 MAP kinase is necessary for NMDA-induced spinal PGE(2) release and thermal hyperalgesia.
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 E(2) (PGE(2)) and thermal hyperalgesia. Inhibition of spinal p38 MAPK attenuated both NMDA-evoked release of PGE(2) 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 PGE(2) release and hyperalgesia, and that microglia is involved in spinal nociceptive processing.
Svensson
Camilla I
CI
Department of Pathology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0612, USA. csvennsson@ucsd.edu
Hua
Xiao-Ying
XY
Protter
Andrew A
AA
Powell
Henry C
HC
Yaksh
Tony L
TL
D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D001253:Astrocytes / Q000378:metabolism; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D003956:Dialysis / Q000379:methods; D015232:Dinoprostone / Q000134:cerebrospinal fluid / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C079432:Bsg protein, rat; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D008562:Membrane Glycoproteins; D051926:Basigin; D016202:N-Methylaspartate; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone