A New Rat Model of Thalamic Pain Produced by Administration of Cobra Venom to the Unilateral Ventral Posterolateral Nucleus.
A New Rat Model of Thalamic Pain Produced by Administration of Cobra Venom to the Unilateral Ventral Posterolateral Nucleus.
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DOI：
10.36076/ppj/2019.22.e635
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发表时间：
2019-11
期刊：
影响因子：
3.7
通讯作者：
Jian-xiong An;Wan-Rui Shi;Jian-Feng Zhang;Xiao-yan Qian;Qi-wu Fang;Yong Wang;John P. Williams
中科院分区：
文献类型：
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作者：
Jian-xiong An;Wan-Rui Shi;Jian-Feng Zhang;Xiao-yan Qian;Qi-wu Fang;Yong Wang;John P. Williams
背景丘脑疼痛是一种由于丘脑损害而发生的神经病理性疼痛综合征。由于丘脑疼痛的机制尚不清楚，因此很难开发出针对丘脑疼痛的治疗干预措施。为了更好地了解丘脑疼痛的病理生理学基础，我们利用向丘脑腹后外侧核(VPL)微量注射眼镜蛇毒素的技术，建立并表征了一种新的丘脑疼痛模型。目的建立单侧腹后外侧核注射眼镜蛇蛇毒致大鼠丘脑疼痛模型。研究设计本研究采用大鼠实验设计。地点：中国医科大学航空总医院和北京转化医学研究所实验室。方法雄性SD大鼠左侧VPL分别注入眼镜蛇蛇毒或生理盐水。分别采用von Frey实验、录像和柱状实验观察大鼠丘脑内微量注射眼镜蛇蛇毒后机械性痛觉过敏的发生、痛相关行为和运动功能的变化。在术后第7到35天，电针和普瑞巴林(PGB)都被用来验证该模型在人类身上重现了这一发现。此外，通过透射电子显微镜观察丘脑的组织结构变化。结果丘脑疼痛模型制作后第3天，左侧面部皮肤对机械刺激的反应阈值较用药前明显降低。在透射电子显微镜下观察神经元超微结构的改变，如神经元核凹陷，线粒体和内质网受损，周围组织溶解。此外，电针治疗还能改善丘脑痛模型大鼠的机械痛觉过敏、痛样行为和运动功能障碍，并恢复正常的神经元结构。然而，当服用PGB时，没有注意到这种有益的影响。限制本模型的病理生理学特征不同于目前的模型和临床实践中的患者(大多数情况下，中风，无论是缺血性的还是出血性的)。结论眼镜蛇蛇毒模型可为丘脑疼痛机制的研究和丘脑损伤后恢复及疼痛靶向治疗试验提供一个合理的模型。关键词丘脑疼痛；眼镜蛇毒素；电针；普瑞巴林；神经元核凹陷；线粒体受损；溶解内质网；高尔基体。
BACKGROUND Thalamic pain is a neuropathic pain syndrome that occurs as a result of thalamic damage. It is difficult to develop therapeutic interventions for thalamic pain because its mechanism is unclear. To better understand the pathophysiological basis of thalamic pain, we developed and characterized a new rat model of thalamic pain using a technique of microinjecting cobra venom into the ventral posterolateral nucleus (VPL) of the thalamus. OBJECTIVES This study will establish a new thalamic pain rat model produced by administration of cobra venom to the unilateral ventral posterolateral nucleus. STUDY DESIGN This study used an experimental design in rats. SETTING The research took place in the laboratory at the Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine. METHODS Male Sprague-Dawley rats were subjected to the administration of cobra venom or saline into the left VPL. The development of mechanical hyperalgesia and changes in pain-related behaviors and motor function were measured after intrathalamic cobra venom microinjection using the von Frey test, video recording, and cylinder test, respectively. On postoperative days 7 to 35, both electroacupuncture and pregabalin (PGB) were administered to verify that the model reproduced the findings in humans. Moreover, the organizational and structural alterations of the thalamus were examined via transmission electron microscopy (TEM). RESULTS The threshold for mechanical stimuli in the left facial skin was significantly decreased on day 3 after thalamic pain modeling as compared with pre-venom treatment. Furthermore, the ultrastructural alterations of neurons such as indented neuronal nuclei, damaged mitochondria and endoplasmic reticulum, and dissolved surrounding tissues were observed under TEM. Moreover, electroacupuncture treatment ameliorated mechanical hyperalgesia, pain-like behaviors, and motor dysfunction, as well as restore normal structures of neurons in the thalamic pain rat model. However, no such beneficial effects were noted when PGB was administered. LIMITATIONS The pathophysiological features were different from the present model and the patients in clinical practice (in most cases strokes, either ischemic or hemorrhagic). CONCLUSION The cobra venom model may provide a reasonable model for investigating the mechanism of thalamic pain and for testing therapies targeting recovery and pain after thalamic lesions. KEY WORDS Thalamic pain, cobra venom, electroacupuncture, pregabalin, indented neuronal nuclei, damaged mitochondria, dissolved endoplasmic reticulum, golgi body.