Development and pharmacological verification of a new mouse model of central post-stroke pain
Development and pharmacological verification of a new mouse model of central post-stroke pain
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DOI：
10.1016/j.neures.2013.09.005
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发表时间：
2014-01-01
影响因子：
2.9
通讯作者：
Miyata, Atsuro
中科院分区：
文献类型：
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作者：
Hanada, Tomoko;Kurihara, Takashi;Miyata, Atsuro
中枢性中风后疼痛（CPSP）包括丘脑疼痛是脑血管意外后可能发生的最棘手的后遗症之一。虽然中风患者中CPSP的患病率相对较低，但持续的、通常是治疗难治性的疼痛感觉可能是一个主要问题，并降低了受影响患者的生活质量。为了更好地了解CPSP的病理生理基础，我们开发了一种新的丘脑CPSP小鼠模型。该模型是基于丘脑腹后外侧核中的胶原酶的出血性中风病变。组织学分析表明，丘脑出血产生了一个相对局限的病变，破坏了初始出血内的组织，也显示了激活的小胶质细胞邻近出血性病变的核心的存在。行为分析表明，动物表现出双氯芬酸，吗啡或普瑞巴林耐机械异常性疼痛和热痛觉过敏的后爪对侧的病变超过112天。然而，我们发现，米诺环素，小胶质细胞抑制剂，显着改善机械异常性疼痛和热痛觉过敏。这些结果表明，该模型可能被证明是一个有用的动物模型，研究丘脑综合征的神经病理学，并开发改进的治疗CPSP。(C)2013 Elsevier爱尔兰有限公司和日本神经科学学会。All rights reserved.
Central post-stroke pain (CPSP) including thalamic pain is one of the most troublesome sequelae that can occur after a cerebrovascular accident. Although the prevalence of CPSP among stroke patients is relatively low, the persistent, often treatment-refractory, painful sensations can be a major problem and decrease the affected patient's quality of life. To better understand of the pathophysiological basis of CPSP, we developed and characterized a new mouse model of thalamic CPSP. This model is based on a hemorrhagic stroke lesion with collagenase in the ventral posterolateral nucleus of the thalamus. Histopathological analysis indicated that the thalamic hemorrhage produced a relatively confined lesion that destroys the tissue within the initial bleed, and also showed the presence of activated microglia adjacent to the core of hemorrhagic lesions. Behavioral analysis demonstrated that the animals displayed diclofenac-, morphine- or pregabalin-resistant mechanical allodynia and thermal hyperalgesia of the hind paw contralateral to the lesion for over 112 days. However, we found that minocycline, a microglial inhibitor, significantly ameliorated mechanical allodynia and thermal hyperalgesia. These results suggest that this model might be proved as a useful animal model for studying the neuropathology of thalamic syndrome, and developing improved therapeutics for CPSP. (C) 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.