Dalziel Robert G, Bingham Sharon, Sutton David, Grant Dawn, Champion Jean M, Dennis Shelley A, Quinn John P, Bountra Chas, Mark Margo A
Center for Infectious Disease, School of Veterinary Medicine, Division of Veterinary Biomedical Sciences, University of Edinburgh, Edinburgh EH9 1QH, UK.
Brain Res Brain Res Rev. 2004 Oct;46(2):234-42. doi: 10.1016/j.brainresrev.2004.07.008.
The most common complication of herpes zoster is post-herpetic neuralgia (PHN), which has been defined as severe pain occurring 1 month after rash onset or persisting for greater than 3 months. PHN is classed as a neuropathic pain that is associated with mechanical allodynia where normally innocuous tactile stimuli are perceived as painful. The development of therapies to treat PHN has been hampered by the lack of animal models, which mimic the clinical situation. We have previously reported that varicella zoster virus (VZV) infection in the rat results in mechanical allodynia and thermal hyperalgesia. Here, we report that following VZV infection of the left footpad rats develop a chronic mechanical allodynia, which is present for longer than 60 days post-infection and which resolves by 100 days PI. The model is robust and reproducible with animals consistently developing allodynia by 3 days PI and continuing to present with symptoms for at least 30 days. The reproducible nature of the induction and course of the allodynia allows the use of this model to determine the effect of various compounds on, and to investigate the pathogenic mechanisms underlying the development of VZV-induced allodynia. Comparative studies using HSV-1 show that the induction of the chronic allodynia is VZV-specific and is not a result is of virus replication-induced tissue damage or accompanying inflammation. Therefore, we propose that the rat VZV infection model could prove useful in studying the mechanisms underlying post-herpetic neuralgia.
带状疱疹最常见的并发症是带状疱疹后神经痛（PHN），其被定义为皮疹发作1个月后出现或持续超过3个月的严重疼痛。PHN被归类为一种神经性疼痛，与机械性异常性疼痛相关，即通常无害的触觉刺激会被感知为疼痛。由于缺乏模拟临床情况的动物模型，治疗PHN的疗法开发受到了阻碍。我们之前报道过，大鼠感染水痘带状疱疹病毒（VZV）会导致机械性异常性疼痛和热痛觉过敏。在此，我们报告，左侧足垫感染VZV后，大鼠会出现慢性机械性异常性疼痛，这种疼痛在感染后60天以上持续存在，并在感染后100天消退。该模型稳定且可重复，动物在感染后3天一致出现异常性疼痛，并至少持续30天出现症状。异常性疼痛诱导和病程的可重复性使得可以使用该模型来确定各种化合物对VZV诱导的异常性疼痛的影响，并研究其发病机制。使用单纯疱疹病毒1型（HSV-1）的对比研究表明，慢性异常性疼痛的诱导是VZV特异性的，并非病毒复制诱导的组织损伤或伴随炎症的结果。因此，我们认为大鼠VZV感染模型可能有助于研究带状疱疹后神经痛的潜在机制。
