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:7254559
- 负责人:
- 金额:$ 18.94万
- 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 2009-01-31
- 项目状态:已结题
- 来源:
- 关键词:Absence EpilepsyAnimalsAnticonvulsantsAntiepileptic AgentsBehavioral AssayBehavioral ParadigmBiologicalBrainBrain StemCellsComplexConditionDeafferentation procedureDejerine Roussy SyndromeDenervationDown-RegulationEthosuximideFiberFigs - dietaryGlutamatesGrantHeadHumanLesionMeasuresModelingNeuronsNociceptionNumbersOutputPainPathologyPathway interactionsPerceptionPharmaceutical PreparationsPotassium ChannelPreventionRattusResistanceRodent ModelSensorySliceSpinal CordSpinal InjuriesSpinothalamic TractsStimulusSynapsesSyndromeTestingThalamic structureTherapeuticUp-RegulationValproic Acidcentral paininjuredneuronal excitabilitypreventresearch studyresponsesynaptic inhibitiontherapeutic targetvoltage
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(由申请人提供):中枢性疼痛综合症(CPS)的特征是由脊髓、脑干或丘脑病变或病变引起的严重且难以忍受的疼痛,并且对任何治疗或药物具有高度抵抗力。其原因尚不清楚。我的目标是开发一种 CPS 啮齿动物模型,通过该模型,我们可以开始了解这种使人衰弱的疾病背后的细胞机制,并测试其治疗和/或预防的潜在有用的治疗靶点。我推测,大鼠或人类脊髓中的上行感觉输入通路的损伤会导致丘脑腹基底复合体中中继细胞的部分去神经支配,从而导致其兴奋性延迟增加。这种过度兴奋可能是由于内在神经元兴奋性增加(例如 K+ 通道下调或 Ca2+ 通道上调)和/或网络兴奋性增加(例如突触抑制或兴奋改变)所致。该假说预测,在失神性癫痫中表现出抗惊厥活性的药物(如乙舒肟)将减少丘脑的过度兴奋性并缓解中枢性疼痛综合征。我将通过研究已建立的行为范式对疼痛的感知,以及脊髓中上行伤害性通路受损的大鼠离体脑切片中丘脑神经元的内在和网络兴奋性来测试这些假设。此外,我将测试乙舒肟和其他“丘脑”抗癫痫药物是否能有效恢复正常的疼痛感知并降低受伤大鼠脑切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破坏性病症的起源的理解,并为迫切需要的治疗缓解指明道路。我将尝试在大鼠中建立中枢性疼痛综合症的模型,这是一种头部或脊髓损伤患者遭受的极度疼痛,以便我们能够了解这种使人衰弱的疾病的生物学原因,并提出治疗或预防这种疾病的新想法。
项目成果
期刊论文数量(0)
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:
$ 18.94万 - 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:
7369672 - 财政年份:2007
- 资助金额:
$ 18.94万 - 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:
$ 18.94万 - 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:
6475435 - 财政年份:2002
- 资助金额:
$ 18.94万 - 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:
$ 18.94万 - 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:
6723646 - 财政年份:2002
- 资助金额:
$ 18.94万 - 项目类别:
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