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 mu g) and NS-398 (7-60 mu g), as well as a high dose (100 mu g) of the COX-I inhibitor SC-560 attenuated hyperalgesia, whereas intrathecal administrations of a low dose (10 mu g) of SC-560 and the COX-3 inhibitor acetaminophen (1-7 mg) did not. Further, intrathecal administration of SC-58125 (100 mu g) 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. (c) 2006 Elsevier B.V. All rights reserved.