Constitutive spinal cyclooxygenase-2 participates in the initiation of tissue injury-induced hyperalgesia.
Inhibitors of the isozyme cyclooxygenase-2 (COX-2) represent an important advance in pain management, although where and when these inhibitors can exert their antihyperalgesic actions are not completely understood. Here we show that unlike many peripheral tissues in which COX-2 is only expressed in physiologically significant levels after tissue injury, in the normal rat lumbar spinal cord, the majority of neurons and radial glia constitutively express high levels of COX-2 protein. Immediately after peripheral tissue injury and before any measurable upregulation of COX-2 protein in peripheral tissue or spinal cord, inhibition of constitutively expressed spinal COX-2 reduced injury-induced activation of primary afferent neurons, activation of spinal neurons, and the mechanical and thermal hyperalgesia that normally occurs after peripheral tissue injury. The present data demonstrate that constitutively expressed spinal COX-2 plays an important role in the initial hyperalgesia that follows peripheral tissue injury. These results suggest that blocking constitutive spinal COX-2 before tissue injury may reduce the initial peripheral and central sensitization that occurs after tissue injury.
Ghilardi
Joseph R
JR
Department of Preventive Sciences and Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Svensson
Camilla I
CI
Rogers
Scott D
SD
Yaksh
Tony L
TL
Mantyh
Patrick W
PW
D000818:Animals; D015153:Blotting, Western; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D006614:Hindlimb / Q000293:injuries / Q000294:innervation / Q000503:physiopathology; D006930:Hyperalgesia / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D007150:Immunohistochemistry; D007278:Injections, Spinal; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D008161:Lumbosacral Region; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009457:Neuroglia / Q000201:enzymology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D010812:Physical Stimulation; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism* / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D013373:Substance P / Q000378:metabolism; D015854:Up-Regulation
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011453:Prostaglandins; D016760:Proto-Oncogene Proteins c-fos; D013373:Substance P; D016202:N-Methylaspartate; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases