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首页> 外文学位 >Peripheral and spinal mechanisms of neuropathic behaviors following peripheral nerve injury.
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Peripheral and spinal mechanisms of neuropathic behaviors following peripheral nerve injury.

机译：周围神经损伤后神经病变行为的周围和脊髓机制。

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摘要

Neuropathic pain describes chronic pain syndromes that follow peripheral nerve injury. This thesis project addressed the hypothesis that both the peripheral and central nervous system contribute to neuropathic pain using a rodent peripheral neuropathy model, sciatic cryoneurolysis (SCN). SCN results in the display of two aberrant behaviors which mimic human neuropathic pain: autotomy (biting the affected limb, thought to represent dysesthesia) and allodynia (increased sensitivity to innocuous stimuli).; Peripheral nerve lesion pathology was serially quantified following SCN. Grid morphometry demonstrated that endoneurial percentages of edema, regenerating axons, and activated macrophages and Schwann cells correlated with initial autotomy. Autotomy behavior paralleled the percentage of macrophages and Schwann cells throughout the study, implicating an influence of local cytokines and/or growth factors. Axon diameter measurements demonstrated that peripheral nerve fiber regeneration of intermediate-sized (presumably A-{dollar}delta ){dollar} fibers corresponded with allodynia.; Allodynia may result from spinal neurochemical changes that disinhibit pain pathways. Serial changes in spinal glutamate, dynorphin, and glial fibrillary acidic protein (GFAP) were monitored immunohistochemically following SCN. These factors were chosen as they are strongly implicated in the development of neuropathic behaviors in other experimental neuropathy models. Following SCN, increased glutamate and dynorphin immunoreactivity coincided with allodynia. However, preemptive pharmacological antagonism of the N-methyl-D-aspartate (NMDA) glutamate receptor or dynorphin function (using anti-dynorphin antibody) did not robustly alter allodynia outcome. Of interest, antagonizing dynorphin function significantly increased immunoreactive glutamate. GFAP cell profiles were also significantly increased at 42 days post-SCN coincident with allodynia. Importantly, cell profiles of non-allodynic animals at 120 days post-SCN were decreased from 42 day values. As GFAP upregulation indicates astrocytic activation, a glial role in the generation of allodynia is implicated.; These studies identified specific peripheral and spinal changes that bear on the pathogenesis of neuropathic behaviors following peripheral nerve injury. In contrast to other neuropathy models, NMDA receptor function was not a prerequisite for abnormal behavior development in SCN. However, common important elements included activation of peripheral macrophages and spinal astrocytes. Antagonizing pathological macrophage and/or Schwann cell activity or abnormal spinal astrocytic activity are potential ubitiquous treatments for human neuropathic pain arising from different peripheral nerve injuries.
机译：神经性疼痛描述了周围神经损伤后的慢性疼痛综合征。本项目解决了以下假设：使用啮齿动物周围神经病模型（坐骨神经冷冻解毒术（SCN）），周围神经系统和中枢神经系统均会导致神经性疼痛。 SCN导致出现两种模仿人类神经性疼痛的异常行为：自动切开术（咬住患肢，被认为代表感觉异常）和异常性疼痛（对无害刺激的敏感性增加）。 SCN后连续定量周围神经病变病理。网格形态学证实，神经内膜水肿，再生轴突，活化的巨噬细胞和雪旺氏细胞的神经内膜百分比与最初的尸体切除术相关。在整个研究中，尸体解剖行为与巨噬细胞和雪旺氏细胞的百分比平行，暗示了局部细胞因子和/或生长因子的影响。轴突直径的测量表明中等大小（大概是A- {dollar} delta）{dollar}纤维的周围神经纤维再生与异常性疼痛相对应。异常性疼痛可能是由于抑制疼痛途径的脊髓神经化学变化引起的。 SCN后，通过免疫组织化学方法监测脊髓谷氨酸，强啡肽和神经胶质纤维酸性蛋白（GFAP）的系列变化。选择这些因素是因为它们在其他实验性神经病模型中与神经病行为的发展密切相关。 SCN后，谷氨酸和强啡肽的免疫反应性增加，与异常性疼痛相吻合。但是，N-甲基-D-天门冬氨酸（NMDA）谷氨酸受体或强啡肽功能（使用抗强啡肽抗体）的先发性药理拮抗作用不能强烈改变异常性疼痛的结局。令人感兴趣的是，拮抗强啡肽功能显着增加了免疫反应性谷氨酸。在SCN后42天与异常性疼痛同时发生时，GFAP细胞谱也显着增加。重要的是，SCN后120天的非异常性动物的细胞分布从42天的值降低了。由于GFAP上调指示星形细胞活化，因此牵涉神经胶质在异常性疼痛产生中的作用。这些研究确定了周围神经损伤后特定的周围和脊柱变化，这些变化影响神经性行为的发病机理。与其他神经病变模型相反，NMDA受体功能不是SCN中异常行为发展的先决条件。但是，常见的重要因素包括外周巨噬细胞和脊髓星形胶质细胞的活化。对抗病理性巨噬细胞和/或雪旺氏细胞活性或异常的脊髓星形胶质细胞活性是潜在的不适当的治疗方法，可用于治疗因不同周围神经损伤而引起的人类神经性疼痛。

著录项

  • 作者

    Wagner, Rochelle.;

  • 作者单位

    Dartmouth College.;

  • 授予单位 Dartmouth College.;
  • 学科 Biology Neuroscience.; Health Sciences Pathology.
  • 学位 Ph.D.
  • 年度 1995
  • 页码 93 p.
  • 总页数 93
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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