Constitutive spinal cyclooxygenase-2 participates in the initiation of tissue injury-induced hyperalgesia
Constitutive spinal cyclooxygenase-2 participates in the initiation of tissue injury-induced hyperalgesia
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DOI：
10.1523/jneurosci.5054-03.2004
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发表时间：
2004-03-17
影响因子：
5.3
通讯作者：
Mantyh, PW
中科院分区：
文献类型：
--
作者：
Ghilardi, JR;Svensson, CI;Mantyh, PW
同工酶环氧合酶-2（考克斯-2）的抑制剂代表了疼痛管理的重要进展，尽管这些抑制剂何时何地发挥其抗痛觉过敏作用尚不完全清楚。在这里，我们表明，不像许多外周组织中，考克斯-2仅在生理上显着的组织损伤后，在正常大鼠腰髓，大多数神经元和放射状胶质细胞组成性表达高水平的考克斯-2蛋白。在外周组织损伤后和外周组织或脊髓中考克斯-2蛋白的任何可测量的上调之前，组成性表达的脊髓考克斯-2的抑制减少了损伤诱导的初级传入神经元的激活、脊髓神经元的激活以及外周组织损伤后通常发生的机械和热痛觉过敏。目前的数据表明，组成性表达的脊髓考克斯-2起着重要的作用，在最初的痛觉过敏，以下周围组织损伤。这些结果表明，在组织损伤前阻断组成性脊髓考克斯-2可减少组织损伤后发生的初始外周和中枢致敏。
Inhibitors of the isozyme cyclooxygenase-2 (COX-2) represent an important advance in pain management, although where and when these inhibitors can exert their antihyperalgesic actions are not completely understood. Here we show that unlike many peripheral tissues in which COX-2 is only expressed in physiologically significant levels after tissue injury, in the normal rat lumbar spinal cord, the majority of neurons and radial glia constitutively express high levels of COX-2 protein. Immediately after peripheral tissue injury and before any measurable upregulation of COX-2 protein in peripheral tissue or spinal cord, inhibition of constitutively expressed spinal COX-2 reduced injury-induced activation of primary afferent neurons, activation of spinal neurons, and the mechanical and thermal hyperalgesia that normally occurs after peripheral tissue injury. The present data demonstrate that constitutively expressed spinal COX-2 plays an important role in the initial hyperalgesia that follows peripheral tissue injury. These results suggest that blocking constitutive spinal COX-2 before tissue injury may reduce the initial peripheral and central sensitization that occurs after tissue injury.