Spinal p38 MAP kinase is necessary for NMDA-induced spinal PGE(2) release and thermal hyperalgesia

Neuroreport. 2003 Jun 11;14(8):1153-7. doi: 10.1097/00001756-200306110-00010.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antigens, CD*
  • Antigens, Neoplasm*
  • Antigens, Surface*
  • Astrocytes / metabolism
  • Avian Proteins*
  • Basigin
  • Blood Proteins*
  • Dialysis / methods
  • Dinoprostone / cerebrospinal fluid
  • Dinoprostone / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Excitatory Amino Acid Agonists / pharmacology
  • Glial Fibrillary Acidic Protein / metabolism
  • Hyperalgesia / metabolism*
  • Immunohistochemistry / methods
  • Male
  • Membrane Glycoproteins / metabolism
  • Microglia / metabolism
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism*
  • N-Methylaspartate / pharmacology*
  • Pain Measurement / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / enzymology*
  • Spinal Cord / metabolism
  • Spinal Cord / physiopathology
  • Time Factors
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Antigens, CD
  • Antigens, Neoplasm
  • Antigens, Surface
  • Avian Proteins
  • Blood Proteins
  • Bsg protein, Gallus gallus
  • Bsg protein, rat
  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Glial Fibrillary Acidic Protein
  • Membrane Glycoproteins
  • Basigin
  • N-Methylaspartate
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Dinoprostone