Intrathecally administered COX-2 but not COX-1 or COX-3 inhibitors attenuate streptozotocin-induced mechanical hyperalgesia in rats.
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.
Matsunaga
Aki
A
Department of Anesthesiology and Critical Care, Division of Clinical Medical Science, Graduate School of Biomedical Science, Hiroshima University. amatsu@hiroshima-u.ac.jp
Kawamoto
Masashi
M
Shiraishi
Seiji
S
Yasuda
Toshimichi
T
Kajiyama
Seiji
S
Kurita
Shigeaki
S
Yuge
Osafumi
O
D000818:Animals; D051545:Cyclooxygenase 1 / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D015232:Dinoprostone / Q000502:physiology; D006930:Hyperalgesia / Q000188:drug therapy*; D007278:Injections, Spinal; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011720:Pyrazoles / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; C115461:SC 560; C090859:1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole; D013311:Streptozocin; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C466421:cyclooxygenase-3; D015232:Dinoprostone