Intrathecal HIV-1 envelope glycoprotein gp120 induces enhanced pain states mediated by spinal cord proinflammatory cytokines
Intrathecal HIV-1 envelope glycoprotein gp120 induces enhanced pain states mediated by spinal cord proinflammatory cytokines
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DOI：
10.1523/jneurosci.21-08-02808.2001
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发表时间：
2001-04-15
影响因子：
5.3
通讯作者：
Watkins, LR
中科院分区：
文献类型：
--
作者：
Milligan, ED;O'Connor, KA;Watkins, LR
脊髓周围（鞘内）注射人类免疫缺陷病毒-1（HIV-1）包膜糖蛋白gp 120可产生夸张的疼痛状态。gp 120给药后，对热刺激（热痛觉过敏）和光触觉刺激（机械性异常性疼痛）的反应阈值迅速降低。gp 120是HIV-1的一部分，结合并激活小胶质细胞和星形胶质细胞。这些胶质细胞被认为是gp 120诱导的痛觉过敏和异常性疼痛的关键介质，因为这些疼痛变化被认为优先影响胶质功能的药物阻断。本系列研究的目的是确定gp 120诱导的疼痛变化是否涉及促炎细胞因子[白细胞介素-1 β（IL-1）和肿瘤坏死因子-α（TNF-α）]。（TNF-α）]，从激活的神经胶质细胞释放的物质。IL-1和TNF拮抗剂各自防止gp 120诱导的疼痛变化。鞘内注射gp 120可使TNF和IL-1蛋白释放到腰骶部CSF中产生时间依赖性、位点特异性增加;同时还观察到腰背部脊髓中细胞因子的平行增加。鞘内注射氟柠檬酸盐（一种神经胶质代谢抑制剂）、TNF拮抗剂和IL-1拮抗剂均能阻断gp 120诱导的脊髓IL-1蛋白增加。这些结果支持了脊髓背侧胶质细胞活化可通过释放促炎细胞因子产生过度疼痛的观点。
Perispinal (intrathecal) injection of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein gp120 creates exaggerated pain states. Decreases in response thresholds to both heat stimuli (thermal hyperalgesia) and light tactile stimuli (mechanical allodynia) are rapidly induced after gp120 administration. gp120 is the portion of HIV-1 that binds to and activates microglia and astrocytes. These glial cells have been proposed to be key mediators of gp120-induced hyperalgesia and allodynia because these pain changes are blocked by drugs thought to affect glial function preferentially The aim of the present series of studies was to determine whether gp120-induced pain changes involve proinflammatory cytokines [interleukin-1 beta (IL-1) and tumor necrosis factor-alpha (TNF-alpha)], substances released from activated glia. IL-1 and TNF antagonists each prevented gp120-induced pain changes. Intrathecal gp120 produced time-dependent, site-specific increases in TNF and IL-1 protein release into lumbosacral CSF; parallel cytokine increases in lumbar dorsal spinal cord were also observed. Intrathecal administration of fluorocitrate (a glial metabolic inhibitor), TNF antagonist, and IL-1 antagonist each blocked gp120-induced increases in spinal IL-1 protein. These results support the concept that activated glia in dorsal spinal cord can create exaggerated pain states via the release of proinflammatory cytokines.