Central Pain Syndrome: Thalamic Hyperexcitability After Denervation?

中枢性疼痛综合征:去神经后丘脑过度兴奋?

基本信息

  • 批准号:
    7369672
  • 负责人:
  • 金额:
    $ 16.24万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2007
  • 资助国家:
    美国
  • 起止时间:
    2007-03-05 至 2010-01-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Central Pain Syndrome (CPS) is characterized by severe and excruciating pain resulting from a lesion or pathology in the spinal cord, brainstem, or thalamus, and is highly resistant to any therapy or medication. Its cause is unknown. My objective is to develop a rodent model of CPS with which we can begin to understand the cellular mechanisms underlying this debilitating condition and test potentially useful therapeutic targets for its treatment and/or prevention. I hypothesize that a lesion of ascending sensory input pathways in the spinal cord of rats or humans causes partial denervation of relay cells in the ventrobasal complex of the thalamus resulting in a delayed increase in their excitability. This hyperexcitability might result from either increased intrinsic neuronal excitability (e.g. a downregulation of K+ channels or upregulation of Ca2+ channels) and/or increased network excitability (e.g. altered synaptic inhibition or excitation). The hypothesis predicts that drugs that display anticonvulsant activity in absence epilepsy, such as ethosuximde, will reduce excessive thalamic excitability and relieve central pain syndrome. I will test these hypotheses by investigating the perception of pain with well established behavioral paradigms, and the intrinsic and network excitability of thalamic neurons in ex vivo brain slices from rats in which ascending nociceptive pathways in the spinal cord have been lesioned. In addition, I will test whether ethosuximde and other 'thalamic' antiepileptic drugs effectively restore normal pain perception and decrease the excitability of thalamic neurons in brain slices from injured rats. These experiments should increase our understanding of the genesis of this devastating condition and point the way to sorely needed therapeutic relief. I will attempt to develop a model of Central Pain Syndrome, a form of excruciating pain suffered by victims of head or spinal injuries, in rats so that we can understand the biological causes of this debilitating condition and suggest new ideas for treating or preventing it.
描述(申请人提供):中枢性疼痛综合征(CPS)的特征是由脊髓、脑干或丘脑的病变或病理引起的严重和极度疼痛,对任何治疗或药物都具有高度抵抗力。其原因尚不清楚。我的目标是建立一种CPS的啮齿动物模型,利用它,我们可以开始了解这种衰弱疾病背后的细胞机制,并测试潜在有用的治疗靶点,用于治疗和/或预防这种疾病。我假设,大鼠或人类脊髓上升感觉输入通路的损伤会导致丘脑腹基复合体中的中继细胞部分去神经,从而导致它们的兴奋性延迟增加。这种超兴奋性可能是由于神经元固有兴奋性的增加(如K+通道的下调或钙通道的上调)和/或网络兴奋性的增加(如改变突触抑制或兴奋)。该假说预测,在失神癫痫中表现出抗惊厥活性的药物,如乙硫昔,将减少丘脑过度兴奋,缓解中枢性疼痛综合征。我将用成熟的行为范式研究痛觉,并研究脊髓上行伤害性通路受损的大鼠体外脑片中丘脑神经元的内在和网络兴奋性,以检验这些假说。此外,我还将测试乙硫胺和其他丘脑抗癫痫药物是否有效地恢复了正常的痛觉,并降低了受伤大鼠脑片中丘脑神经元的兴奋性。这些实验应该会增加我们对这种毁灭性疾病的起源的理解,并为迫切需要的治疗缓解指明方向。我将尝试在大鼠身上建立中枢疼痛综合症的模型,这是头部或脊柱损伤的受害者遭受的一种折磨人的疼痛形式,这样我们就可以了解这种虚弱疾病的生物学原因,并提出治疗或预防它的新想法。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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SCOTT M. THOMPSON其他文献

SCOTT M. THOMPSON的其他文献

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{{ truncateString('SCOTT M. THOMPSON', 18)}}的其他基金

Stress, depression and effects of novel antidepressants on excitatory synapses
压力、抑郁和新型抗抑郁药对兴奋性突触的影响
  • 批准号:
    9270600
  • 财政年份:
    2010
  • 资助金额:
    $ 16.24万
  • 项目类别:
Central Pain Syndrome: Thalamic Hyperexcitability After Denervation?
中枢性疼痛综合征:去神经后丘脑过度兴奋?
  • 批准号:
    7254559
  • 财政年份:
    2007
  • 资助金额:
    $ 16.24万
  • 项目类别:
Pre and Postsynaptic Consequences of Traumatic CNS Injury
中枢神经系统损伤的突触前和突触后后果
  • 批准号:
    7991811
  • 财政年份:
    2002
  • 资助金额:
    $ 16.24万
  • 项目类别:
Plasticity of Hippocampal Structure and Function
海马结构和功能的可塑性
  • 批准号:
    6623055
  • 财政年份:
    2002
  • 资助金额:
    $ 16.24万
  • 项目类别:
Axonal Sprouting and Epilepsy after Traumatic CNS Injury
中枢神经系统外伤后的轴突出芽和癫痫
  • 批准号:
    6875711
  • 财政年份:
    2002
  • 资助金额:
    $ 16.24万
  • 项目类别:
Plasticity of Hippocampal Structure and Function
海马结构和功能的可塑性
  • 批准号:
    6701759
  • 财政年份:
    2002
  • 资助金额:
    $ 16.24万
  • 项目类别:
Pre and Postsynaptic Consequences of Traumatic CNS Injury
中枢神经系统损伤的突触前和突触后后果
  • 批准号:
    7383287
  • 财政年份:
    2002
  • 资助金额:
    $ 16.24万
  • 项目类别:
Axonal Sprouting and Epilepsy after Traumatic CNS Injury
中枢神经系统外伤后的轴突出芽和癫痫
  • 批准号:
    6624509
  • 财政年份:
    2002
  • 资助金额:
    $ 16.24万
  • 项目类别:
Plasticity of Hippocampal Structure and Function
海马结构和功能的可塑性
  • 批准号:
    7015029
  • 财政年份:
    2002
  • 资助金额:
    $ 16.24万
  • 项目类别:
Plasticity of Hippocampal Structure and Function
海马结构和功能的可塑性
  • 批准号:
    6460681
  • 财政年份:
    2002
  • 资助金额:
    $ 16.24万
  • 项目类别:

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