Mediators of C-Fiber Response to Partial Nerve Injury

C 纤维对部分神经损伤反应的调节因子

基本信息

  • 批准号:
    7233215
  • 负责人:
  • 金额:
    $ 17.02万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2006
  • 资助国家:
    美国
  • 起止时间:
    2006-05-16 至 2011-04-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Peripheral neuropathy is a major clinical problem that afflicts about 20 million persons in the U.S. alone. Pain is a prominent feature and it is generally stubbornly resistant to treatment. Our preliminary data have shown that transection of the 5th lumbar ventral root (L5 Ventral Rhizotomy) in rat results in pain behavior, altered C-fiber electrophysiology, and changes in C-fiber cell biology. In the L5 Ventral Rhizotomy model of neuropathic pain, C-fiber sensory axons are not directly injured but respond briskly to degeneration of nearby motor axons. The degenerating and uninjured axons co-mingle in peripheral nerve but do not interact directly in the spinal cord, sensory ganglion or skin. Our central hypothesis is: Degenerating axons in the peripheral nerve signal uninjured C-fibers via diffusible factors and that this leads to neuropathic pain. SPECIFIC AIM 1 is to determine the role of peripheral nerve interactions between uninjured and degenerating axons in neuropathic pain behavior. This will be studied using a newly developed model of neuropathic pain that implants a degenerating nerve segment from an inbred donor over a fenestration in the sciatic nerve of a recipient animal. A complementary approach will be taken by minimizing peripheral nerve interactions using L3 ventral rhizotomy; in general, L3 axons do not enter the sciatic nerve. SPECIFIC AIM 2 is to examine the response of uninjured C-fibers to degenerating axons in peripheral nerve using these same models. The responses of uninjured C-fibers will be measured as changes in C-fiber conduction velocity properties and increased mitosis of nonmyelinating Schwann cells. SPECIFIC AIM 3 will assess the role of NGF, as a potential diffusible factor released after nerve injury that is responsible for pain behavior and neuropathic C-fiber change. This will be studied by translating the above methods into mouse species and studying the responses to these same models in a strain of mice that has inducible inhibition of signaling through the TrkA, high-affinity NGF receptor. The long term objectives of this research are to identify therapeutic targets for the treatment of neuropathic pain. This research will be conducted during a period of mentored career development emphasizing advanced skills in pain research and the responsible conduct of science.
描述(由申请人提供):周围神经病变是一个主要的临床问题,仅在美国就有约2000万人受到折磨。疼痛是一个突出的特点,它通常是顽固地抵抗治疗。我们的初步数据表明,大鼠第5腰腹根横断(L5腰神经切断术)导致疼痛行为、C纤维电生理学改变和C纤维细胞生物学变化。在神经病理性疼痛的L5神经根切断术模型中,C纤维感觉轴突没有直接损伤,而是对附近运动轴突的变性迅速作出反应。变性和未损伤的轴突在周围神经中混合,但在脊髓、感觉神经节或皮肤中不直接相互作用。我们的中心假设是:周围神经中的变性轴突通过扩散因子向未受伤的C纤维发出信号,这导致神经性疼痛。具体目的1是确定未损伤和退化轴突之间的外周神经相互作用在神经病理性疼痛行为中的作用。这将使用一种新开发的神经性疼痛模型进行研究,该模型将来自近交系供体的变性神经段植入受体动物坐骨神经的开窗处。通过使用L3腹根切断术最大限度地减少外周神经相互作用,将采取补充方法;通常,L3轴突不会进入坐骨神经。具体目的2是使用这些相同的模型检查未损伤的C纤维对周围神经中变性轴突的反应。未损伤的C纤维的反应将被测量为C纤维传导速度特性的变化和非髓鞘化雪旺细胞的有丝分裂增加。具体目标3将评估神经生长因子的作用,作为神经损伤后释放的潜在扩散因子,负责疼痛行为和神经病理性C纤维变化。这将通过将上述方法翻译到小鼠物种中并研究在具有通过TrkA(高亲和力NGF受体)的信号传导的诱导性抑制的小鼠品系中对这些相同模型的响应来研究。本研究的长期目标是确定治疗神经性疼痛的治疗靶点。这项研究将在指导职业发展期间进行,强调疼痛研究的先进技能和负责任的科学行为。

项目成果

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会议论文数量(0)
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BETH B HOGANS其他文献

BETH B HOGANS的其他文献

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{{ truncateString('BETH B HOGANS', 18)}}的其他基金

Evidence-Based Multidimensional Pain Self-Management Planning: Personalized by and for Veterans via Web-Based Application
基于证据的多维疼痛自我管理规划:通过基于网络的应用程序由退伍军人个性化并为退伍军人提供个性化服务
  • 批准号:
    10461704
  • 财政年份:
    2020
  • 资助金额:
    $ 17.02万
  • 项目类别:
Evidence-Based Multidimensional Pain Self-Management Planning: Personalized by and for Veterans via Web-Based Application
基于证据的多维疼痛自我管理规划:通过基于网络的应用程序由退伍军人个性化并为退伍军人提供个性化服务
  • 批准号:
    9891456
  • 财政年份:
    2020
  • 资助金额:
    $ 17.02万
  • 项目类别:
Evidence-Based Multidimensional Pain Self-Management Planning: Personalized by and for Veterans via Web-Based Application
基于证据的多维疼痛自我管理规划:通过基于网络的应用程序由退伍军人个性化并为退伍军人提供个性化服务
  • 批准号:
    10053684
  • 财政年份:
    2020
  • 资助金额:
    $ 17.02万
  • 项目类别:
Mediators of C-Fiber Response to Partial Nerve Injury
C 纤维对部分神经损伤反应的调节因子
  • 批准号:
    7809509
  • 财政年份:
    2006
  • 资助金额:
    $ 17.02万
  • 项目类别:
Mediators of C-Fiber Response to Partial Nerve Injury
C 纤维对部分神经损伤反应的调节因子
  • 批准号:
    7428819
  • 财政年份:
    2006
  • 资助金额:
    $ 17.02万
  • 项目类别:
Mediators of C-Fiber Response to Partial Nerve Injury
C 纤维对部分神经损伤反应的调节因子
  • 批准号:
    7029813
  • 财政年份:
    2006
  • 资助金额:
    $ 17.02万
  • 项目类别:
Mediators of C-Fiber Response to Partial Nerve Injury
C 纤维对部分神经损伤反应的调节因子
  • 批准号:
    7665127
  • 财政年份:
    2006
  • 资助金额:
    $ 17.02万
  • 项目类别:

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