Department of Ophthalmology, University of Pittsburgh, 203 Lothrop Street, Pittsburgh, PA, 15213, USA.
Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
Curr Top Microbiol Immunol. 2023;438:189-221. doi: 10.1007/82_2021_240.
Reactivation of latent varicella-zoster virus (VZV) causes herpes zoster (HZ), which is commonly accompanied by acute pain and pruritus over the time course of a zosteriform rash. Although the rash and associated pain are self-limiting, a considerable fraction of HZ cases will subsequently develop debilitating chronic pain states termed postherpetic neuralgia (PHN). How VZV causes acute pain and the mechanisms underlying the transition to PHN are far from clear. The human-specific nature of VZV has made in vivo modeling of pain following reactivation difficult to study because no single animal can reproduce reactivated VZV disease as observed in the clinic. Investigations of VZV pathogenesis following primary infection have benefited greatly from human tissues harbored in immune-deficient mice, but modeling of acute and chronic pain requires an intact nervous system with the capability of transmitting ascending and descending sensory signals. Several groups have found that subcutaneous VZV inoculation of the rat induces prolonged and measurable changes in nociceptive behavior, indicating sensitivity that partially mimics the development of mechanical allodynia and thermal hyperalgesia seen in HZ and PHN patients. Although it is not a model of reactivation, the rat is beginning to inform how VZV infection can evoke a pain response and induce long-lasting alterations to nociception. In this review, we will summarize the rat pain models from a practical perspective and discuss avenues that have opened for testing of novel treatments for both zoster-associated pain and chronic PHN conditions, which remain in critical need of effective therapies.
潜伏的水痘带状疱疹病毒 (VZV) 的激活会导致带状疱疹 (HZ)，HZ 通常伴有带状疱疹样皮疹过程中的急性疼痛和瘙痒。尽管皮疹和相关疼痛是自限性的，但相当一部分 HZ 病例随后会发展为衰弱的慢性疼痛状态，称为带状疱疹后神经痛 (PHN)。VZV 如何引起急性疼痛以及向 PHN 转变的机制还远不清楚。VZV 的人类特异性使得难以研究其激活后疼痛的体内模型，因为没有一种动物可以复制临床上观察到的 VZV 再激活疾病。对原发性感染后 VZV 发病机制的研究极大地受益于免疫缺陷小鼠中携带的人类组织，但急性和慢性疼痛的建模需要一个完整的神经系统，能够传递上行和下行感觉信号。有几个研究小组发现，大鼠的皮下 VZV 接种会引起长时间和可测量的痛觉行为变化，表明其敏感性部分模拟了 HZ 和 PHN 患者中机械性痛觉过敏和热痛觉过敏的发展。尽管它不是一种再激活模型，但大鼠开始告知我们 VZV 感染如何引起疼痛反应，并诱导对伤害性感受的持久改变。在这篇综述中，我们将从实用的角度总结大鼠疼痛模型，并讨论为带状疱疹相关疼痛和慢性 PHN 状况的新型治疗方法的测试开辟的途径，这些状况仍然迫切需要有效的治疗方法。
