Spinal p38 mitogen-activated protein kinase mediates allodynia induced by first-degree burn in the rat.
Activation of p38 mitogen-activated protein kinase (MAPK) in the spinal cord has been implicated in the development and maintenance of pain states. In this study, we tested whether p38 MAPK is involved in the response to first-degree burn of the hind paw. This injury induces central sensitization leading to tactile allodynia and is mediated by activation of Ca(2+) permeable AMPA/kainate receptors through PKC and PKA. We demonstrate that p38 MAPK is rapidly and robustly activated in the superficial spinal dorsal horn after mild thermal injury to the hind paw. Activated p38 MAPK was localized primarily to microglia and to a lesser extent in oligodendrocytes and lamina II neurons. Astrocytes were not involved in the p38 MAPK response. Intrathecal pretreatment of pharmacological inhibitors of p38 MAPK (SB203580, SD-282) dose-dependently blocked development of tactile allodynia, a characteristic of the first-degree burn model. The effects of the inhibitors on tactile allodynia were lost when they were administered after injury. These studies identify p38 MAPK as a major mediator of tactile allodynia, most likely activated downstream of AMPA/kainate receptors.
Department of Anesthesiology, University of California-San Diego, La Jolla, California, USA. lsorkin@ucsd.edu
Linda
L
Sorkin
Camilla I
CI
Svensson
Toni L
TL
Jones-Cordero
Michael P
MP
Hefferan
W Marie
WM
Campana
D000818:Animals; D002056:Burns / Q000201:enzymology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D007093:Imidazoles / Q000008:administration & dosage; D007211:Indoles / Q000008:administration & dosage; D008297:Male; D017628:Microglia / Q000201:enzymology; D009474:Neurons / Q000201:enzymology; D009836:Oligodendroglia / Q000201:enzymology; D010146:Pain / Q000188:drug therapy / Q000201:enzymology*; D010766:Phosphorylation; D011725:Pyridines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007093:Imidazoles; D007211:Indoles; D011725:Pyridines; C514526:indole-5-carboxamide; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580