Cyclooxygenase-1 in the spinal cord plays an important role in postoperative pain.
Cyclooxygenase-2 (COX-2) activity in the spinal cord plays a key role in sensitization to sensory stimuli during acute inflammation. In contrast, intrathecal administration of COX-2 specific inhibitors has minimal analgesic effects in an incisional model of postoperative pain. We investigated the role of COX isoforms in this model by examining the expression of COX-1 and the effect of intrathecal COX inhibitors. A 1cm longitudinal incision was made through skin, fascia and muscles of the plantar aspect of the left paw in male rats, and withdrawal threshold to von Frey filaments measured. Rats were perfused at 1, 2, 3, 5, and 7 days after incision, and COX-1 immunohistochemistry was performed on L3 to S2 spinal cord and gracile nucleus sections. Other rats received intrathecally the COX-1 preferring inhibitor, ketorolac, the specific COX-1 inhibitor, SC-560, the COX-2 inhibitor, NS-398 or vehicle 1 day after surgery. Withdrawal threshold was measured at intervals up to 5 days later. COX-1 immunoreactivity increased in glia in the ipsilateral L4-L6 spinal dorsal horn and ipsilateral gracile nucleus after incision. Mechanical allodynia peaked on postoperative day 1, and COX-1 immunoreactivity increased on day 1, peaked on day 2, and declined thereafter. Ketorolac and SC-560 dose-dependently increased withdrawal threshold in this model, but NS-398 had no effect. These results suggest that COX-1 plays an important role in spinal cord pain processing and sensitization after surgery. Increased COX-1 activity could precede the up-regulation of COX-1 protein, and spinally administered specific COX-1 inhibitors may be useful to treat postoperative pain.
Zhu
Xiaoying
X
Program of Neuroscience, Department of Anesthesiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. xzhu@wfubmc.edu
Conklin
Dawn
D
Eisenach
James C
JC
D000818:Animals; D051545:Cyclooxygenase 1; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010149:Postoperative Pain / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology*
D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat