Role for both spinal cord COX-1 and COX-2 in maintenance of mechanical hypersensitivity following peripheral nerve injury.
The effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) in treating neuropathic pain caused by nerve injury has been controversial. In the present study, 4 weeks following partial sciatic nerve ligation, a single intrathecal injection of the cyclooxygenase (COX)-1 preferring inhibitor ketorolac (50 microg) significantly attenuated tactile allodynia for 6 days. The COX-2 preferring inhibitor, NS-398 (60 microg) significantly reversed tactile allodynia 2 h following injection but this anti-allodynic effect did not last greater than 24 h. Surprisingly, the non-selective COX inhibitor, piroxicam (60 microg) was without effect. These data agree with previous studies suggesting that spinal prostaglandin synthesis is important in the maintenance of hypersensitivity states following nerve injury. They differ from results in other models by suggesting that both COX isoenzymes are important in this spinal process, and for the first time demonstrate a remarkably long duration of action from a single intrathecal injection of ketorolac. Inhibition of spinal COX may be an important mechanism of action in treating some patients with neuropathic pain following peripheral nerve injury.
Ma
Weiya
W
Pain Mechanisms Laboratory, Department of Anesthesiology and Center for the Study of Pharmacologic Plasticity in the Presence of Pain, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1009, USA. wma@wfubmc.edu
Du
Wei
W
Eisenach
James C
JC
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006930:Hyperalgesia / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D020910:Ketorolac / Q000494:pharmacology; D008026:Ligation; D008465:Mechanoreceptors / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D009578:Nitrobenzenes / Q000494:pharmacology; D010894:Piroxicam / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries*; D013116:Spinal Cord / Q000201:enzymology* / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D010894:Piroxicam; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D020910:Ketorolac