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Research Progress on the Animal Models of Neuromyelitis Optica Spectrum Disorders-related Neuropathic Pain
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摘要: 视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disorders, NMOSD)是一种中枢神经系统炎性脱髓鞘性疾病，临床特征包括视神经炎、纵向长节段脊髓炎及其引起的疼痛，其中以神经病理性疼痛最为常见。目前已有研究证实神经病理性疼痛在NMOSD动物模型中存在，但受限于动物模型的缺乏，疼痛机制尚不明确，未来亟需建立可靠且简便易行的NMOSD神经病理性疼痛动物模型，以阐明发病机制，探索有效的预防及治疗策略。本文就NMOSD动物模型的建立及疼痛机制的研究进展作一综述，以期为建立理想的NMOSD神经病理性疼痛动物模型提供参考。
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关键词:
- 视神经脊髓炎谱系疾病 /
- 脱髓鞘性疾病 /
- 神经病理性疼痛 /
- 动物模型
Abstract: Neuromyelitis optica spectrum disorders(NMOSD), an inflammatory demyelinating disease of central nervous system, is characterized by optic neuritis, longitudinally extensive transverse myelitis, and neuropathic pain. Given the lack of mature animal models, the mechanism of neuropathic pain in NMOSD is still unclear, although some studies have reported neuropathic pain in NMOSD models. It is therefore necessary to build a reliable and feasible animal model of NMOSD related neuropathic pain, in order to provide scientific support for the mechanism and the mining of therapeutic targets. This article reviews the research progress of the establishment of NMOSD-related neuropathic pain animal models and their applications, and provides a reference for the establishment of ideal NMOSD neuropathic pain animal models.作者贡献：宋淑佳负责查阅文献资料、撰写论文；裴丽坚、徐雁、张雪、黄宇光负责指导论文撰写、提出修改意见。利益冲突：所有作者均声明不存在利益冲突 -
表 1 NMOSD动物模型及其特征
文献 动物 模型 病变位置 AQP4缺失 GFAP缺失 炎性细胞浸润 补体沉积 脱髓鞘 AQP4-IgG剂量 注射后观察时间点 行为表现 疼痛表现 Kinoshita等[19] 雌性Lewis大鼠 EAE+NMO-IgG腹腔注射 脊髓 是 是 巨噬细胞、中性粒细胞、嗜酸性粒细胞 是 否 20 mg/d×4 d 4 d EAE评分增加 - Chan等[18] 雌性C57BL/6小鼠 EAE+NMO-IgG腹腔注射 脊髓 是 否 否 否 否 2 mg/d×3 d 4 d EAE评分为0 - Saini等[20] 雌性C57/BL6小鼠 EAE+ NMO-IgG+补体腹腔注射 脊髓、视神经 是 是 T细胞、粒细胞 - 是 10 mg 0~60 d EAE评分增加 - Kurosawa等[16] 雌性Lewis大鼠 EAE+ AQP4单克隆抗体(E5415)腹腔注射 脊髓 是 是 中性粒细胞 是 是 1 mg 2 d EAE评分增加 机械痛阈值降低持续至建模后21 d Luo等[21] 雌性C57BL/6 WT小鼠 EAE+MELFUS+NMO-IgG+补体静脉注射 脊髓、大脑和视神经 是 是 单核细胞 是 是 100 μg 7 d - - Saadoun等[24] CD1小鼠 NMO-IgG+补体颅内注射 大脑 是 是 单核细胞 是 是 6~38 g/L，16.8 μL 12 h/7 d 右转 - Asavapanumas等[27] Lewis大鼠 NMO-IgG颅内注射 大脑 是 是 中性粒细胞、巨噬细胞 是 是 10 μg 5 d - - Marignier等[28] 雄性OFA大鼠 NMO-IgG持续颅内注射 大脑、脊髓、视神经 是 否 轻微 否 是 400 μg 3、7、10、14、21 d 运动协调性变差 - Lee等[25] 雌性C57BL/6小鼠 EAE+NMO-IgG+补体重复鞘内注射 大脑、脊髓 是 是 - 是 - 0.6 g/L, 10 μL 0~21 d EAE评分增加 - Zhang等[26] CD59敲除小鼠 NMO-IgG+补体鞘内注射 脊髓 是 是 巨噬细胞/小胶质细胞、中性粒细胞 是 是 10 μg 2 d 后肢无力 - Geis等[30] 雌性Lewis大鼠 NMO-IgG鞘内注射 脊髓 是 是 导管尖端有巨噬细胞轻微浸润 否 否 100 g/L或12 g/L，10 μL×15 d 19 d 后肢不对称性麻痹 - Harada等[29] Wistar大鼠 NMO-IgG鞘内注射 脊髓 是 是 T细胞、小胶质细胞 - 否 20 μg 0~30 d 后肢麻痹 - Ishikura等[23] 雌性Lewis大鼠 抗AQP4重组抗体脊髓注射 脊髓 是 是 - - - 20 μg 1~28 d 无 机械痛阈值降低7 d恢复，热痛阈值无改变 Zeka等[31] Lewis大鼠 AQP4特异性T细胞转运+NMO-IgG腹腔注射 视神经、大脑、脊髓 是 是 T细胞、小胶质细胞和巨噬细胞 是 是 10 mg 7 d 尾部张力丧失 - Matsumoto等[32] SD大鼠 NMO-IgG视神经鞘下注射 视神经、视网膜 是 是 CD11+细胞 - 是 2 μL 7~14 d - - NMOSD: 视神经脊髓炎谱系疾病；AQP4：水通道蛋白4；GFAP：胶质纤维酸性蛋白；EAE：实验性自身免疫性脑脊髓炎；MELFUS：微泡增强低频超声；-：未提及 
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