Thermal hyperalgesia and mechanical allodynia produced by intrathecal administration of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein, gp120
Thermal hyperalgesia and mechanical allodynia produced by intrathecal administration of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein, gp120
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DOI：
10.1016/s0006-8993(00)02050-3
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发表时间：
2000-04-07
期刊：
影响因子：
2.9
通讯作者：
Watkins, LR
中科院分区：
文献类型：
--
作者：
Milligan, ED;Mehmert, KK;Watkins, LR
脊髓中的星形胶质细胞和小胶质细胞最近被报道有助于外周炎症诱导的夸张疼痛状态的发展，热痛阈降低（热痛觉过敏）和对光触觉刺激的反应阈降低（机械性异常性疼痛）都已被报道。脊髓胶质细胞是这种作用的潜在介质的概念是基于被认为优先影响胶质细胞功能的药物对这些夸大的疼痛状态的破坏。星形胶质细胞和小胶质细胞的激活可以释放许多已知介导热痛觉过敏和机械异常性疼痛的相同物质。本系列研究的目的是确定是否夸大的疼痛状态也可以在大鼠中创建的星形胶质细胞和小胶质细胞的直接，脊髓内免疫激活。使用的免疫刺激是脊髓周围（鞘内，i.t.）人类免疫缺陷病毒1型（HIV-1）包膜糖蛋白gp120的应用。已知HIV-1的这一部分结合并激活小胶质细胞和星形胶质细胞。在i.t.反应中观察到强烈的热痛觉过敏（甩尾、TF和Hargreaves测试）和机械性异常性疼痛（von Frey和触摸诱发的激动测试）gp120。gp120复合蛋白结构的热变性阻断gp120诱导的热痛觉过敏。最后，无论是热痛觉过敏和机械异常性疼痛，以i.t. gp120被阻断脊髓预处理药物（氟柠檬酸和CNI-1493）被认为是优先破坏神经胶质功能。(C)2000 Elsevier Science B.V.保留所有权利。
Astrocytes and microglia in the spinal cord have recently been reported to contribute to the development of peripheral inflammation-induced exaggerated pain states, Both lowering of thermal pain threshold (thermal hyperalgesia) and lowering of response threshold to light tactile stimuli (mechanical allodynia) have been reported. The notion that spinal cord glia are potential mediators of such effects is based on the disruption of these exaggerated pain states by drugs thought to preferentially affect glial function. Activation of astrocytes and microglia can release many of the same substances that are known to mediate thermal hyperalgesia and mechanical allodynia. The aim of the present series of studies was to determine whether exaggerated pain states could also be created in rats by direct, intraspinal immune activation of astrocytes and microglia. The immune stimulus used was peri-spinal (intrathecal, i.t.) application of the Human Immunodeficiency Virus type 1 (HIV-1) envelope glycoprotein, gp120. This portion of HIV-1 is known to bind to and activate microglia and astrocytes. Robust thermal hyperalgesia (tail-flick, TF, and Hargreaves tests) and mechanical allodynia (von Frey and touch-evoked agitation tests) were observed in response to i.t. gp120. Heat denaturing of the complex protein structure of gp120 blocked gp 120-induced thermal hyperalgesia. Lastly, both thermal hyperalgesia and mechanical allodynia to i.t. gp120 were blocked by spinal pretreatment with drugs (fluorocitrate and CNI-1493) thought to preferentially disrupt glial function. (C) 2000 Elsevier Science B.V. All rights reserved.