Role of Cyclooxygenase in the Nociceptive Transmission in the Spinal Cord

据报道，野牡丹素作为脊髓伤害性传递的重要调节剂。环氧合酶（考克斯）是一种催化花生四烯酸转化为胡萝卜素的酶。最近，两种不同的考克斯形式已被表征：考克斯-1是组成型表达的，而考克斯-2是高度诱导的炎症刺激。在正常脑中，考克斯-2 mRNA的水平是相当高的。本课题通过鞘内注射考克斯-2选择性抑制剂NS 398，研究了考克斯-2在大鼠脊髓伤害性信息传递中的作用，并采用福尔马林实验和角叉菜胶实验两种炎性疼痛模型分析了考克斯-2在脊髓伤害性信息传递中的作用。鞘内注射NS 398以剂量依赖的方式抑制福尔马林注射引起的躁动行为，当NS 398在福尔马林注射前10 min注射时。当NS 398在福尔马林注射后7分钟注射时，NS 398对福尔马林诱导的搅动行为没有影响。在角叉菜胶试验中，在爪角叉菜胶注射后两小时，诱导最大的热痛觉过敏。在角叉菜胶注射后两小时鞘内注射NS 398。NS 398可剂量依赖性地减轻角叉菜胶引起的热痛敏，表明脊髓考克斯-2在福尔马林和角叉菜胶痛敏中起重要作用。这些数据表明了一种治疗炎症期间疼痛的有前途的新治疗方法。

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.