Stinson Crystal, Deng Mohong, Yee Michael B, Bellinger Larry L, Kinchington Paul R, Kramer Phillip R
Department of Biomedical Sciences, Texas A&M University College of Dentistry, 3302 Gaston Avenue, Dallas, TX, 75246, USA.
Department of Oral and Maxillofacial Surgery, The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
BMC Neurol. 2017 May 17;17(1):95. doi: 10.1186/s12883-017-0882-6.
Most people are initially infected with varicella zoster virus (VZV) at a young age and this infection results in chickenpox. VZV then becomes latent and reactivates later in life resulting in herpes zoster (HZ) or "shingles". Often VZV infects neurons of the trigeminal ganglia to cause ocular problems, orofacial disease and occasionally a chronic pain condition termed post-herpetic neuralgia (PHN). To date, no model has been developed to study orofacial pain related to varicella zoster. Importantly, the incidence of zoster associated pain and PHN is known to be higher in women, although reasons for this sex difference remain unclear. Prior to this work, no animal model was available to study these sex-differences. Our goal was to develop an orofacial animal model for zoster associated pain which could be utilized to study the mechanisms contributing to this sex difference.
To develop this model VZV was injected into the whisker pad of rats resulting in IE62 protein expression in the trigeminal ganglia; IE62 is an immediate early gene in the VZV replication program.
Similar to PHN patients, rats showed retraction of neurites after VZV infection. Treatment of rats with gabapentin, an agent often used to combat PHN, ameliorated the pain response after whisker pad injection. Aversive behavior was significantly greater for up to 7 weeks in VZV injected rats over control inoculated rats. Sex differences were also seen such that ovariectomized and intact female rats given the lower dose of VZV showed a longer affective response than male rats. The phase of the estrous cycle also affected the aversive response suggesting a role for sex steroids in modulating VZV pain.
These results suggest that this rat model can be utilized to study the mechanisms of 1) orofacial zoster associated pain and 2) the sex differences underlying zoster associated pain.
大多数人在幼年时初次感染水痘带状疱疹病毒（VZV），这种感染会导致水痘。随后，VZV会潜伏下来，并在日后重新激活，引发带状疱疹（HZ）或“缠腰龙”。VZV常常感染三叉神经节的神经元，从而导致眼部问题、口腔面部疾病，偶尔还会引发一种称为带状疱疹后神经痛（PHN）的慢性疼痛病症。迄今为止，尚未开发出用于研究与水痘带状疱疹相关的口腔面部疼痛的模型。重要的是，已知带状疱疹相关疼痛和PHN的发病率在女性中更高，尽管这种性别差异的原因尚不清楚。在这项研究之前，没有可用于研究这些性别差异的动物模型。我们的目标是开发一种用于带状疱疹相关疼痛的口腔面部动物模型，该模型可用于研究导致这种性别差异的机制。
为了建立这个模型，将VZV注射到大鼠的须垫中，导致三叉神经节中IE62蛋白表达；IE62是VZV复制程序中的一个立即早期基因。
与PHN患者相似，大鼠在VZV感染后出现神经突回缩。用加巴喷丁（一种常用于治疗PHN的药物）治疗大鼠，可改善须垫注射后的疼痛反应。在长达7周的时间里，注射VZV的大鼠的厌恶行为明显比接种对照的大鼠更强烈。还观察到了性别差异，即给予较低剂量VZV的去卵巢和未去卵巢雌性大鼠比雄性大鼠表现出更长时间的情感反应。发情周期阶段也影响厌恶反应，表明性类固醇在调节VZV疼痛中起作用。
这些结果表明，这个大鼠模型可用于研究1）口腔面部带状疱疹相关疼痛的机制和2）带状疱疹相关疼痛背后的性别差异机制。
