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Leptin is essential for microglial activation and neuropathic pain after preganglionic cervical root avulsion

机译:瘦素对于PREGanglionic宫颈根撕裂后的显微胶质激活和神经性疼痛至关重要

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Abstract Aims Preganglionic cervical root avulsion (PCRA) affects both the peripheral and central nervous systems and is often associated with neuropathic pain. Unlike peripheral nerve injuries (PNI), central lesions caused by disruption of cervical roots from the spinal cord following PCRA contribute to the generation of neuropathic pain. Leptin is involved in the development of neuropathic pain after PNI by affecting neurons. However, whether leptin is involved in microglial activation leading to neuropathic pain after PCRA is unknown. Main methods Preganglionic avulsion of the left 6 th –8 th cervical roots was performed in C57B/6 J mice and leptin-deficient mice. A leptin antagonist or leptin was administered to C57B/6 J mice and leptin-deficient mice after injury, respectively. The expression pattern of spinal and supraspinal microglia was examined by immunofluorescent staining. Von Frey filaments were used to test pain sensitivity. Key findings Leptin is essential for the development of neuropathic pain after PCRA. Allodynia was absent in the leptin-deficient mice and the mice administered the leptin antagonist. We also found that leptin deficiency or the administration of its antagonist inhibited the development of microgliosis in the dorsal horn and brainstem. Furthermore, increase in the expression of CD86 and iNOS, and Wallerian degeneration were noted in the spinal cord. The administration of exogenous leptin to leptin-deficient mice reversed these effects. Significance We concluded that leptin is involved in the proliferation and activation of microglia, which in turn enhances the development of neuropathic pain. Blocking the effects of leptin might be a target for the treatment of neuropathic pain after PCRA.
机译:摘要目的普遍宫颈根撕裂(PCRA)影响外周和中枢神经系统,通常与神经性疼痛有关。与外周神经损伤(PNI)不同,由PCRA后由脊髓中断引起的中央病变导致神经性疼痛的产生。通过影响神经元,瘦素参与PNI后神经病疼痛的发展。然而,在PCRA未知后,瘦素是否参与导致神经性疼痛的显微痛激活。主要方法在C57B / 6 J小鼠和瘦蛋白缺陷小鼠中进行左6六-8周宫颈根的PREGanglionic撕血。损伤后施用瘦素拮抗剂或瘦蛋白在C57B / 6J小鼠和瘦蛋白缺陷小鼠中。通过免疫荧光染色检查脊柱和袋袋脊髓胶质细胞的表达模式。 von Frey丝用来测试疼痛敏感性。主要发现瘦素对于PCRA后神经病疼痛的发展至关重要。在瘦素缺陷的小鼠中不存在异育虫,小鼠施用瘦素拮抗剂。我们还发现,瘦素缺乏或其拮抗剂的给药抑制了背角和脑干中微细胞分泌的发育。此外,在脊髓中注意到CD86和InOS的表达和Wallerian变性的增加。外源性瘦素对瘦蛋白缺乏小鼠的给药逆转了这些效果。我们得出的意义,瘦素参与了微胶质细胞的增殖和激活,这反过来增强了神经性疼痛的发展。阻断瘦素的效果可能是治疗PCRA后神经病疼痛的靶标。

著录项

  • 来源
    《Life sciences》 |2017年第2017期|共11页
  • 作者单位

    Institute of Pharmacology School of Medicine National Yang-Ming University;

    Neural Regeneration Laboratory Department of Neurosurgery Neurological Institute Taipei Veterans;

    Neural Regeneration Laboratory Department of Neurosurgery Neurological Institute Taipei Veterans;

    Neural Regeneration Laboratory Department of Neurosurgery Neurological Institute Taipei Veterans;

    Neural Regeneration Laboratory Department of Neurosurgery Neurological Institute Taipei Veterans;

    Neural Regeneration Laboratory Department of Neurosurgery Neurological Institute Taipei Veterans;

    Department of Neurosurgery Neurological Institute Taipei Veterans General Hospital;

    Division of Pediatric Neurosurgery Neurological Institute Taipei Veterans General Hospital;

    Institute of Pharmacology School of Medicine National Yang-Ming University;

    Neural Regeneration Laboratory Department of Neurosurgery Neurological Institute Taipei Veterans;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 医药、卫生;
  • 关键词

    Leptin; Microglia; Neuropathic pain; Root avulsion;

    机译:瘦素;小胶质细胞;神经性疼痛;根撕裂;

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