Varicella zoster virus-induced pain and post-herpetic neuralgia in the human host and in rodent animal models
Varicella zoster virus-induced pain and post-herpetic neuralgia in the human host and in rodent animal models
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DOI：
10.1007/s13365-011-0069-7
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发表时间：
2011-12-01
影响因子：
3.2
通讯作者：
Goins, William F.
中科院分区：
文献类型：
--
作者：
Kinchington, Paul R.;Goins, William F.
疼痛和带状疱疹后神经痛(PHN)是带状疱疹常见的高度痛苦的并发症，仍然是一个重大的公共卫生问题，需要改进治疗方法。带状疱疹是由于疱疹病毒水痘带状疱疹病毒(VZV)在初次感染(水痘)时建立的神经元潜伏状态重新激活所致。PHN发生在约五分之一至三分之一的带状疱疹病例中，其严重程度、发病率和疼痛持续时间随着患者年龄的增加而增加。虽然VZV的重新激活和随之而来的神经节损伤触发了疼痛反应，但延迟性PHN背后的机制尚不清楚，而且缺乏带状疱疹(重新激活)的动物模型使这一问题更具挑战性。最近开发了一种临床前啮齿动物模型，为探索VZV诱发疼痛的潜在机制和治疗提供了可能。将活体细胞相关的人VZV接种到大鼠的后爪后，大鼠可以可靠地表现出较长时间的热痛敏和机械性超敏，然后自然恢复。背根神经节表达有限的VZV基因亚群，包括IE62调节蛋白，并上调提示神经病理性疼痛状态的标志物的表达。该模型已被用于研究疼痛信号的治疗方式和方面，作者正在进行研究，以描绘与疼痛诱导有关的VZV遗传学。这篇文章将人类带状疱疹相关疼痛和PHN与大鼠的疼痛指标进行了比较，并提出了一些重要的问题，如果得到回答，可能会成为新的治疗方法的基础。
Pain and post-herpetic neuralgia (PHN) are common and highly distressing complications of herpes zoster that remain a significant public health concern and in need of improved therapies. Zoster results from reactivation of the herpesvirus varicella zoster virus (VZV) from a neuronal latent state established at the primary infection (varicella). PHN occurs in some one fifth to one third of zoster cases with severity, incidence, and duration of pain increasing with rising patient age. While VZV reactivation and the ensuing ganglionic damage trigger the pain response, the mechanisms underlying protracted PHN are not understood, and the lack of an animal model of herpes zoster (reactivation) makes this issue more challenging. A recent preclinical rodent model has developed that opens up the potential to allow the exploration of the underlying mechanisms and treatments for VZV-induced pain. Rats inoculated with live cell-associated human VZV into the hind paw reliably demonstrate thermal hyperalgesia and mechanical allodynia for extended periods and then spontaneously recover. Dorsal root ganglia express a limited VZV gene subset, including the IE62 regulatory protein, and upregulate expression of markers suggesting a neuropathic pain state. The model has been used to investigate treatment modalities and aspects of pain signaling and is under investigation by the authors to delineate VZV genetics involved in the induction of pain. This article compares human zoster-associated pain and PHN to the pain indicators in the rat and poses important questions that, if answered, could be the basis for new treatments.