Role of spinal p38alpha and beta MAPK in inflammatory hyperalgesia and spinal COX-2 expression.
Pharmacological studies indicate that spinal p38 mitogen-activated protein kinase plays a role in the development of hyperalgesia. We investigated whether either the spinal isoform p38alpha or p38beta is involved in peripheral inflammation evoked pain state and increased expression of spinal COX-2. Using intrathecal antisense oligonucleotides, we show that hyperalgesia is prevented by downregulation of p38beta but not p38alpha, whereas increases in spinal COX-2 protein expression at 8 hours are mediated by both p38alpha and beta isoforms. These data suggest that early activation of spinal p38beta isoform may affect acute facilitatory processing, and both p38beta and alpha isoforms mediate temporally delayed upregulation of spinal COX-2.
Department of Anesthesiology, University of California-San Diego, California, USA.
Bethany L
BL
Fitzsimmons
Michela
M
Zattoni
Camilla I
CI
Svensson
Joanne
J
Steinauer
Xiao-Ying
XY
Hua
Tony L
TL
Yaksh
D000818:Animals; D015153:Blotting, Western; D002351:Carrageenan / Q000008:administration & dosage / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control*; D007249:Inflammation; D007278:Injections, Spinal; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D020033:Protein Isoforms; D002351:Carrageenan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; D048051:p38 Mitogen-Activated Protein Kinases