Intrathecally administered COX-2 but not COX-1 or COX-3 inhibitors attenuate streptozotocin-induced mechanical hyperalgesia in rats.

Abstract

Members of the cyclooxygenase (COX) family are known to catalyze the rate-limiting steps of prostaglandins synthesis and reported to be involved in neuropathic pain. Diabetic neuropathy is a type of neuropathic pain, though it is not clear if COX is relevant to the condition. Recently, spinal COX-2 protein was found to be increasing in streptozotocin-induced rats as compared to the constitutive expression. We attempted to determine which cyclooxygenase isoforms are involved in streptozotocin-induced mechanical hyperalgesia, which was induced by a single intraperitoneal injection of 75 mg/kg of streptozotocin. Intrathecal administrations of the COX-2 inhibitors SC-58125 (7-100 microg) and NS-398 (7-60 microg), as well as a high dose (100 microg) of the COX-1 inhibitor SC-560 attenuated hyperalgesia, whereas intrathecal administrations of a low dose (10 microg) of SC-560 and the COX-3 inhibitor acetaminophen (1-7 mg) did not. Further, intrathecal administration of SC-58125 (100 microg) did not produce an analgesic effect in normal rats. These results indicate that intrathecal administration of COX-2 inhibitors has an anti-hyperalgesic effect on streptozotocin-induced mechanical hyperalgesia and we concluded that spinal COX-2 is pivotal in streptozotocin-induced hyperalgesia.

• Authors: Aki Matsunaga, Masashi Kawamoto, Seiji Shiraishi, Toshimichi Yasuda, Seiji Kajiyama, Shigeaki Kurita, Osafumi Yuge
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 554 Issue 1 Pg. 12-7 (Jan 05 2007) ISSN: 0014-2999 [Print] Netherlands
• PMID: 17112505 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclooxygenase Inhibitors
• Pyrazoles
• SC 560
• 1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole
• Streptozocin
• Cyclooxygenase 1
• Cyclooxygenase 2
• Prostaglandin-Endoperoxide Synthases
• cyclooxygenase-3
• Dinoprostone

Topics

• Animals
• Cyclooxygenase 1 (physiology)
• Cyclooxygenase 2 (physiology)
• Cyclooxygenase Inhibitors (administration & dosage)
• Diabetes Mellitus, Experimental (complications)
• Diabetic Nephropathies (drug therapy)
• Dinoprostone (physiology)
• Hyperalgesia (drug therapy)
• Injections, Spinal
• Male
• Prostaglandin-Endoperoxide Synthases (physiology)
• Pyrazoles (administration & dosage)
• Rats
• Rats, Sprague-Dawley
• Streptozocin