Varicella zoster virus induces neuropathic changes in rat dorsal root ganglia and behavioral reflex sensitisation that is attenuated by gabapentin or sodium channel blocking drugs
Varicella zoster virus induces neuropathic changes in rat dorsal root ganglia and behavioral reflex sensitisation that is attenuated by gabapentin or sodium channel blocking drugs
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DOI：
10.1016/j.pain.2005.08.003
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发表时间：
2005-11-01
期刊：
影响因子：
7.4
通讯作者：
Fleetwood-Walker, SM
中科院分区：
文献类型：
--
作者：
Garry, EM;Delaney, A;Fleetwood-Walker, SM
感觉三叉神经节和背根神经节（DRG）神经元内潜伏的水痘带状疱疹病毒（VZV）的再活化产生带状疱疹（带状疱疹），通常伴有慢性神经性疼痛状态，疱疹后神经痛（PHN）。PHN持续存在，尽管潜伏期的病毒在人类感觉神经节内，往往是不响应目前的止痛剂或抗病毒药。为了研究水痘带状疱疹引起疼痛的基础，我们利用了最近开发的啮齿动物慢性VZV感染模型。VZV感染后DRG的免疫组织化学分析显示存在与A-（神经丝-200; NF-200）和C-（外周蛋白）传入感觉神经元的标记物共表达的病毒立即早期基因蛋白（IE62）。在共表达NF-200的神经元中，神经肽Y（NPY）的表达增加。此外，VZV感染大鼠DRG中α 2 δ 1钙通道、Na（v）1.3和Na（v）1.8钠通道、神经肽甘丙肽和神经损伤标记物激活转录因子-3（ATF-3）的表达增加，如通过蛋白质印迹法所测定。VZV感染诱导增加的行为反射反应性的伤害性热和机械刺激同侧注射（持续长达10周后感染），这是由脊髓NMDA受体介导的。这些变化被加巴喷丁或钠通道阻滞剂，美西律和拉莫三嗪的全身给药逆转，但不是由非甾体抗炎药，双氯芬酸。这是第一次在啮齿动物中显示VZV感染诱导的DRG表型变化的特征，并揭示该特征似乎与其他神经性疼痛模型中的变化大致相似（但不相同）。(c)2005年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
Reactivation of latent varicella zoster virus (VZV) within sensory trigerninal and dorsal root ganglia (DRG) neurons produces shingles (zoster), often accompanied by a chronic neuropathic pain state, post-herpetic neuralgia (PHN). PHN persists despite latency of the virus within human sensory ganglia and is often unresponsive to current analgesic or antiviral agents. To study the basis of varicella zoster-induced pain, we have utilised a recently developed model of chronic VZV infection in rodents. lmmunohistochemical analysis of DRG following VZV infection showed the presence of a viral immediate early gene protein (IE62) co-expressed with markers of A- (neurofilament-200; NF-200) and C- (peripherin) afferent sensory neurons. There was increased expression of neuropeptide Y (NPY) in neurons co-expressing NF-200. In addition, there was an increased expression of alpha 2 delta 1 calcium channel, Na(v)1.3 and Na(v)1.8 sodium channels, the neuropeptide galanin and the nerve injury marker, Activating Transcription Factor-3 (ATF-3) as determined by Western blotting in DRG of VZV-infected rats. VZV infection induced increased behavioral reflex responsiveness to both noxious thermal and mechanical stimuli ipsilateral to injection (lasting up to 10 weeks post-infection) that is mediated by spinal NMDA receptors. These changes were reversed by systemic administration of gabapentin or the sodium channel blockers, mexiletine and lamotrigine, but not by the non-steroidal anti-inflammatory agent, diclofenac. This is the first time that the profile of VZV infection-induced phenotypic changes in DRG has been shown in rodents and reveals that this profile appears to be broadly similar (but not identical) to changes in other neuropathic pain models. (c) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.