Lateral thalamic control of nociceptive response after whisker pad injection of varicella zoster virus.
Lateral thalamic control of nociceptive response after whisker pad injection of varicella zoster virus.
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DOI：
10.1016/j.neuroscience.2017.05.030
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发表时间：
2017-07-25
期刊：
影响因子：
3.3
通讯作者：
Kinchington PR
中科院分区：
文献类型：
--
作者：
Kramer PR;Stinson C;Umorin M;Deng M;Rao M;Bellinger LL;Yee MB;Kinchington PR
疼痛是带状疱疹（HZ）感染的常见并发症，其由潜伏的水痘带状疱疹病毒（VZV）重新激活引起。三分之一的HZ患者进展为慢性疼痛状态，称为带状疱疹后神经痛（PHN），其中约四分之一的患者有口面疼痛。控制疼痛反应的机制尚不清楚。研究表明，涉及丘脑的中枢通路可以控制与HZ相关的疼痛，本实验室的研究表明，外侧丘脑的囊泡GABA转运体（VGAT）影响口面疼痛。我们假设丘脑VGAT的功能，部分，以减少疼痛，特别是口面疼痛，与VZV。为了解决这一假设，将VZV注射到晶须垫中。疼痛的情感和动机方面进行了测量使用的地方逃避/回避范式。在注射表达工程化乙酰胆碱Gi-蛋白偶联受体的腺相关病毒（AAV）后调节丘脑神经元活性。该受体在与氯氮平-n-氧化物（CNO）结合时抑制神经元放电。通过注射表达VGAT沉默shRNA的AAV构建体来减弱丘脑中的VGAT表达。雄性大鼠给予CNO后，VZV诱导的伤害性感受显著降低。在VGAT表达减弱后，伤害性感受显著增加，同时丘脑c-fos表达增加。这些数据表明，外侧丘脑（后，腹后内侧，腹后外侧和/或网状丘脑核）控制VZV诱导的伤害性感受在口面部区域，在这个区域的GABA似乎减少响应VZV诱导的伤害性感受可能通过门控面部疼痛输入。
Pain is a common complication of herpes zoster (HZ) infection which results from reactivation of a latent varicella zoster virus (VZV). A third of HZ patients’ progress to a chronic pain state known as post herpetic neuralgia (PHN), and about a quarter of these patients’ have orofacial pain. The mechanisms controlling the pain responses are not understood. Studies suggest central pathways involving the thalamus could control pain related to HZ, and studies in our lab suggest vesicular GABA transporter (VGAT) in the lateral thalamus influences orofacial pain. We hypothesized that thalamic VGAT functions, in part, to reduce pain, particularly orofacial pain, associated with VZV. To address this hypothesis VZV was injected into the whisker pad. Affective and motivational aspects of pain were measured using the Place Escape/Avoidance Paradigm. Thalamic neuronal activity was modulated after injecting an adeno-associated virus (AAV) expressing an engineered acetylcholine Gi-protein coupled receptor. This receptor inhibits neuronal firing when bound by clozapine-n-oxide (CNO). VGAT expression was attenuated in the thalamus by injecting an AAV construct that expressed a VGAT silencing shRNA. VZV induced nociception was significantly decreased after administering CNO in male rats. Nociception significantly increased concomitant with increased thalamic c-fos expression after attenuating thalamic VGAT expression. These data establish that the lateral thalamus (posterior, ventral posteromedial, ventral posterolateral and/or reticular thalamic nucleus) controls VZV induced nociception in the orofacial region, and that GABA in this region appears to reduce the response to VZV induced nociception possibly by gating facial pain input.
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DOI：
10.1073/pnas.0700293104
发表时间：
2007-03-20
影响因子：
11.1
作者：
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影响因子：
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作者：
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