Role of Cyclooxygenase in the Nociceptive Transmission in the Spinal Cord

有报道称，前列腺素是脊髓伤害性信息传递的重要调节剂。环氧合酶(COX)是一种催化花生四烯酸转化为前列腺素的酶。最近，两种不同形式的COX已被表征：COX-1是结构性表达的，而COX-2是高度诱导的，对炎症刺激的反应。在正常大脑中，COX-2mRNA的表达水平很高。在本研究中，我通过鞘内注射COX-2选择性抑制剂NS398来研究COX-2在大鼠脊髓伤害性传递中的作用。采用福尔马林实验和Carageenan实验两种炎性疼痛模型分析了COX-2在脊髓伤害性传递中的作用。鞘内注射NS398可剂量依赖地抑制福尔马林致痛小鼠的激越行为，且呈剂量依赖性。在福尔马林注射7min后注射NS398，对福尔马林诱导的激越行为无影响。在Carageenan实验中，在注射爪状Carageenan两小时后，诱导出最大的热痛觉过敏。角叉菜胶注射后2小时鞘内注射NS398。NS398以剂量依赖的方式减轻角叉菜胶注射引起的热痛觉过敏。这些数据表明，脊髓COX-2在大鼠福尔马林实验和角叉菜胶实验中在脊髓伤害性信息传递中起重要作用。这些数据表明，一种很有希望的治疗炎症期间疼痛的新方法。

It has been reported that prostaglandins act as an important modulator of the spinal nociceptive transmission. Cyclooxygenase (COX) is an enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. Recently, two different COX forms have been characterized : COX-1 is constitutively expressed and COX-2 is highly inducible in response to inflammatory stimuli. In the normal brain, the level of COX-2 mRNA is substantial. In this project, I investigated the role of COX-2 in the nociceptive transmission in the rat spinal cord by intrathecal injection of NS398, a COX-2 selective inhibitor.Two inflammatory pain models were used for the analysis of role of COX-2 in the nociceptive transmission in the spinal cord, formalin test and carageenan test. Intrathecal injection of NS398 depressed the agitation behavior induced by paw formalin injection in a dose-dependent manner when NS398 was injected 10 min before the formalin injection. When NS398 was injected 7 min after the formalin injection, NS398 had no effect on the formalin induced agitation behavior. In the carageenan test, two hours after the paw carageenan injection, maximum thermal hyperalgesia was induced. NS398 was injected intrathecally two hours after the carageenan injection. NS398 attenuated the level of thermal hyperalgesia induced by carageenan injection in a dose dependent manner.These data demonstrated that spinal COX-2 plays an important role in spinal nociceptive transmission during the rat formalin test and carageenan test. These data suggested a promising new therapeutic approach to treating pain during inflammation.