A Chronic fatigue syndrome model demonstrates mechanical allodynia and muscular hyperalgesia via spinal microglial activation
A Chronic fatigue syndrome model demonstrates mechanical allodynia and muscular hyperalgesia via spinal microglial activation
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DOI：
10.1002/glia.22687
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发表时间：
2014-09
期刊：
影响因子：
6.2
通讯作者：
Masaya Yasui;T. Yoshimura;So Takeuchi;Kyohei Tokizane;M. Tsuda;Kazuhide Inoue;H. Kiyama
中科院分区：
文献类型：
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作者：
Masaya Yasui;T. Yoshimura;So Takeuchi;Kyohei Tokizane;M. Tsuda;Kazuhide Inoue;H. Kiyama
慢性疲劳综合征（CFS）和纤维肌痛综合征（FMS）患者表现出多种症状，例如慢性广泛疼痛、疲劳、睡眠障碍和认知功能障碍。异常疼痛感可能是这些症状中最严重的。然而，其病理生理学仍然未知。为了深入了解 CFS 和 FMS 异常疼痛的分子基础，我们在大鼠中使用了多重连续应激 (CS) 模型，将其饲养在低水位（1.5 厘米深）的笼子中。 von Frey 和 Randall-Seritto 测试用于评估疼痛水平。结果表明，CS 负荷会引起足底皮肤的机械性痛觉过敏和胫骨前肌的机械性痛觉过敏（即肌肉疼痛）。此外，足底皮肤和腿部肌肉均未观察到炎症和损伤事件的迹象。然而，在 CS 大鼠的 L4-L6 背角中观察到小胶质细胞的积累和激活。定量分析显示，背角 I-IV 层内侧部分的小胶质细胞积累较多。为了评估小胶质细胞对疼痛的影响，鞘内注射米诺环素（通过渗透泵）。米诺环素显着减弱 CS 引起的机械痛觉过敏和异常性疼痛。这些结果表明，激活的小胶质细胞参与了 CS 动物异常疼痛的发生，这表明在 CFS 和 FMS 患者中观察到的疼痛可能部分是由小胶质细胞激活所涉及的机制引起的。 GLIA 2014；62：1407–1417
Patients with chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS) display multiple symptoms, such as chronic widespread pain, fatigue, sleep disturbance, and cognitive dysfunction. Abnormal pain sensation may be the most serious of these symptoms; however, its pathophysiology remains unknown. To provide insights into the molecular basis underlying abnormal pain in CFS and FMS, we used a multiple continuous stress (CS) model in rats, which were housed in a cage with a low level of water (1.5 cm in depth). The von Frey and Randall–Seritto tests were used to evaluate pain levels. Results showed that mechanical allodynia at plantar skin and mechanical hyperalgesia at the anterior tibialis (i.e., muscle pain) were induced by CS loading. Moreover, no signs of inflammation and injury incidents were observed in both the plantar skin and leg muscles. However, microglial accumulation and activation were observed in L4–L6 dorsal horn of CS rats. Quantification analysis revealed a higher accumulation of microglia in the medial part of Layers I–IV of the dorsal horn. To evaluate an implication of microglia in pain, minocycline was intrathecally administrated (via an osmotic pump). Minocycline significantly attenuated CS‐induced mechanical hyperalgesia and allodynia. These results indicated that activated microglia were involved in the development of abnormal pain in CS animals, suggesting that the pain observed in CFS and FMS patients may be partly caused by a mechanism in which microglial activation is involved. GLIA 2014;62:1407–1417