Role of spinal microglia in rat models of peripheral nerve injury and inflammation

Role of spinal microglia in rat models of peripheral nerve injury and inflammation
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DOI:
10.1016/j.ejpain.2006.02.003
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发表时间:
2007-02-01
影响因子:
3.6
通讯作者:
Malcangio, Marzia
Malcangio, Marzia
中科院分区:
医学2区
文献类型:
--
作者:
Clark, Anna K.;Gentry, Clive;Malcangio, Marzia

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越来越多的证据支持脊髓小胶质细胞调节某些慢性疼痛状态的发展和维持的假设。在这里,我们研究了脊髓小胶质细胞在周围炎性损伤和周围神经损伤后的作用。我们观察到损伤后2周同侧背角小胶质细胞显著激活,神经损伤后50天双侧激活,以及足底内酶促后24天双侧激活,但足底内完全弗氏佐剂(CFA)不激活。同侧而非对侧小胶质细胞的激活与后爪机械性痛觉过敏有关。脊髓注射神经胶质代谢灭活剂氟柠檬酸可减轻周围神经损伤后同侧痛觉过敏和双侧脊髓小胶质细胞的激活。足底酶溶后,鞘内氟柠檬酸盐可逆转痛觉过敏,但对cfa诱导的痛觉过敏无逆转作用。这些数据表明脊髓胶质细胞在周围神经损伤后机械性痛觉过敏的持续中起作用。然而,对侧脊髓小胶质细胞的激活与伤害感觉无关。此外,似乎小胶质细胞激活的时间过程及其对炎症性疼痛的贡献取决于给予的炎症刺激。(C) 2006年国际疼痛研究协会欧洲分会联合会。Elsevier Ltd.出版。版权所有。
Mounting evidence supports the hypothesis that spinal microglia modulate the development and maintenance of some chronic pain states. Here we examined the role of spinal microglia following both peripheral inflammatory insult and peripheral nerve injury. We observed significant ipsilateral dorsal horn microglia activation 2 weeks after injury and bilateral activation 50 days following nerve injury as well as 24 It following intraplantar zymosan but not intraplantar complete Freund's adjuvant (CFA). Ipsilateral but not contralateral microglia, activation was associated with hind paw mechanical hyperalgesia. Spinal injection of the glial metabolic inactivator fluorocitrate attenuated ipsilateral hyperalgesia and bilateral spinal microglia activation after peripheral nerve injury. Intrathecal fluorocitrate reversed hyperalgesia after intraplantar zymosan and produced no reversal of CFA-induced hyperalgesia. These data suggest a role for spinal glia in the persistence of mechanical hyperalgesia following peripheral nerve injury. However, activation of spinal microglia contralaterally did not correlate to nociception. Furthermore, it would appear that the time course of microglia activation and their contribution to inflammatory pain is dependent on the inflammatory stimulus administered. (C) 2006 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.