Spinal cyclooxygenase-2 is involved in development of allodynia after nerve injury in rats.
Increased spinal cyclooxygenase activity is associated with nociception induced by tissue inflammation. In the present study, we examined the changes of cyclooxygenase-1 and cyclooxygenase-2 protein expression in several regions of the CNS associated with pain perception, and the role of spinal cyclooxygenase activity in the development of allodynia following nerve injury. Allodynia was induced by ligation of the left L5 and L6 spinal nerves in rats. Using western blot analysis, we found that the cyclooxygenase-2 protein levels in the dorsal spinal cord and thalamus (but not in the ventral spinal cord, cingulate cortex and locus coeruleus) increased significantly one day after nerve ligation, compared with those in the sham animals. The cyclooxygenase-2 protein levels in the above tissues were similar in nerve-injured and sham animals three and 14 days after surgery. In contrast, cyclooxygenase-1 protein was not detectable in any of the neural tissues examined one, three, and 14 days after nerve injury. In the behavioral experiments, we observed that intrathecal injection of 100microg of indomethacin immediately or one day after nerve ligation attenuated the development of tactile allodynia. However, intrathecal injection of indomethacin had no effect on established allodynia two weeks after nerve injury.Collectively, our results suggest that cyclooxygenase-2 is preferentially up-regulated in the dorsal spinal cord and thalamus in response to nerve injury in rats. Spinal cyclooxygenase-2 probably plays an important role in the early development, but not in the maintenance, of tactile allodynia caused by the nerve injury in this rat model of neuropathic pain.
Zhao
Z
Z
Department of Anesthesiology,Wake Forest University School of Medicine, NC 27157, Winston-Salem, USA.
Chen
S R
SR
Eisenach
J C
JC
Busija
D W
DW
Pan
H L
HL
D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D006179:Gyrus Cinguli / Q000201:enzymology; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007278:Injections, Spinal; D007527:Isoenzymes / Q000378:metabolism*; D008125:Locus Coeruleus / Q000201:enzymology; D008297:Male; D008565:Membrane Proteins; D010146:Pain / Q000201:enzymology / Q000503:physiopathology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D013127:Spinal Nerves / Q000293:injuries / Q000503:physiopathology*; D013788:Thalamus / Q000201:enzymology; D013997:Time Factors
D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D007213:Indomethacin