Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation
Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation
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DOI：
10.1016/j.pain.2005.02.009
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发表时间：
2005-05-01
期刊：
影响因子：
7.4
通讯作者：
Watkins, LR
中科院分区：
文献类型：
--
作者：
Ledeboer, A;Sloane, EM;Watkins, LR
脊髓中活化的胶质细胞（小胶质细胞和星形胶质细胞）通过释放促炎细胞因子和其他被认为促进疼痛传递的物质，在介导增强的疼痛状态中发挥重要作用。在本研究中，我们报告鞘内给予米诺环素，一种选择性的小胶质细胞活化抑制剂，抑制低阈值机械异常性痛，通过von Frey试验测量，在两种疼痛促进模型中。在由坐骨神经炎症引起的神经性疼痛大鼠模型中，米诺环素延缓了急性和持续性异位性疼痛的诱导。此外，二甲胺四环素能够在第一天减轻已建立的sin诱导的异常性疼痛，但在一周后却不能，这表明小胶质细胞激活在更持久的疼痛状态中的作用有限。我们的数据与小胶质细胞在启动而不是维持增强的疼痛反应中的关键作用是一致的。在鞘内HIV-1 gp 120脊髓免疫激活模型中，我们发现米诺环素的抗异动作用与小胶质细胞激活降低、腰背脊髓中白细胞介素-1 （IL-1）、肿瘤坏死因子- α (tnf - α)、IL-1 β转换酶、tnf - α转换酶、IL-1受体拮抗剂和IL-10 mRNA表达减弱以及CSF中IL-1 β和tnf - α水平降低有关。二甲胺四环素对gp120诱导的脊髓IL-6和环氧化酶-2表达及脑脊液IL-6水平无显著影响。综上所述，这些数据强调了小胶质细胞激活在过度疼痛状态发展中的重要性。(c) 2005年国际疼痛研究协会。Elsevier B.V.版权所有。
Activated glial cells (microglia and astroglia) in the spinal cord play a major role in mediating enhanced pain states by releasing proinflammatory cytokines and other substances thought to facilitate pain transmission. In the present study, we report that intrathecal administration of minocycline, a selective inhibitor of microglial cell activation, inhibits low threshold mechanical allodynia, as measured by the von Frey test, in two models of pain facilitation. In a rat model of neuropathic pain induced by sciatic nerve inflammation (sciatic inflammatory neuropathy, SIN), minocycline delayed the induction of allodynia in both acute and persistent paradigms. Moreover, minocycline was able to attenuate established SIN-induced allodynia I day, but not I week later, suggesting a limited role of microglial activation in more perseverative pain states. Our data are consistent with a crucial role for microglial cells in initiating, rather than maintaining, enhanced pain responses. In a model of spinal immune activation by intrathecal HIV-1 gp 120, we show that the anti-allodynic effects of minocycline are associated with decreased microglial activation, attenuated mRNA expression of interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), IL-1 beta-converting enzyme, TNF-alpha-converting enzyme, IL-1 receptor antagonist and IL-10 in lumbar dorsal spinal cord, and reduced IL-1 beta and TNF-alpha levels in the CSF In contrast, no significant effects of minocycline were observed on gp120-induced IL-6 and cyclooxygenase-2 expression in spinal cord or CSF IL-6 levels. Taken together these data highlight the importance of microglial activation in the development of exaggerated pain states. (c) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.