PRIMITIVE FOUNDATIONS OF NEUROPATHIC HYPERALGESIA
PRIMITIVE FOUNDATIONS OF NEUROPATHIC HYPERALGESIA
批准号:
2396575
负责人:
EDGAR T. WALTERS
金额:
$17.73万
依托单位国家:
美国
项目类别:
财政年份:
1997
资助国家:
美国
项目状态:
已结题
起止时间:
1997-08-01 至 2000-04-30
中文摘要
描述:总体目标是使用一个简单的无脊椎动物模型
创伤性神经病变敏化以探索基本的细胞机制
这可能是神经性痛觉过敏的重要底物--一种常见的
是人类顽固性和慢性疼痛的组成部分。各种观察结果,
除了进化论,还有一些基本的机制
神经病理性敏化可能是广泛保守的。已确定
伤害性感受器和其他控制尾部退缩反射的神经元
软体动物,海兔,提供了一个特殊的机会来测试
特定的细胞介质在诱导、表达和
终止涉及神经损伤的神经病理性敏感化。使用这个
系统,一种涉及挤压伤的神经病理性敏化模型
Tail将被开发出来,允许直接测试关于
表达和诱导持续性行为和性激素的机制
持续数月的感官变化。测试将进行以下测试
外周改变的贡献,包括传入的敏化,
受损轴突的自发放电与背景神经调节剂
放手。持续性中枢变化的测试将检查过度兴奋
伤害性感受器胞体、中间神经元和运动神经元的易化
中枢突触、去抑制、背景电突触和突触
活动。诱导机制的测试将检验FAST、
活动依赖信号、神经调节剂释放、长时程突触
增强和减慢轴浆信号。关于这个问题的一个普遍假设
CAMP、钙离子和慢速轴浆损伤信号的联合作用
持续性伤害性感受器超兴奋性的诱导和增强
伤害性感受器的再生将在减少的神经节准备中进行测试
和神经,以及在细胞培养中生长的孤立的伤害性感受器。其他
潜在的细胞内和细胞外信号诱导和
持续性伤害性感受器过度兴奋性的维持将开始
在单个细胞中进行筛选。
英文摘要
DESCRIPTION: The general objective is to use a simple invertebrate model of
traumatic neuropathic sensitization to probe fundamental cellular mechanisms
that may be important substrates for neuropathic hyperalgesia--a common
component of intractable and chronic pain in humans. Various observations,
as well as evolutionary arguments, suggest that some basic mechanisms of
neuropathic sensitization are likely to be widely conserved. Identified
nociceptors and other neurons controlling the tail withdrawal reflex in the
mollusc, Aplysia californica, provide a special opportunity to test the
roles of specific cellular mediators in the induction, expression, and
termination of neuropathic sensitization involving nerve injury. Using this
system, a model of neuropathic sensitization involving crush injury of the
tail will be developed that allows direct tests of hypotheses about
mechanisms underlying expression and induction of persistent behavioral and
sensory alterations lasting for months. Tests will be made of the
contributions of peripheral changes, including sensitization of afferents,
spontaneous discharge of injured axons, and background neuromodulator
release. Tests of persistent central changes will examine hyperexcitability
of nociceptor somata, interneurons and motor neurons, facilitation of
central synapses, disinhibition, and background electrical and synaptic
activity. Tests of induction mechanisms will examine contributions of fast,
activity-dependent signals, neuromodulator release, long-term synaptic
potentiation, and slow axoplasmic signals. A general hypothesis about the
combined role of cAMP, calcium ions and slow axoplasmic injury signals in
the induction of persistent nociceptor hyperexcitability and enhancement of
nociceptor regeneration will be tested in a reduced preparation of ganglia
and nerves, and in isolated nociceptors growing in cell culture. Other
potential intracellular and extracellular signals for induction and
maintenance of persistent nociceptor hyperexcitability will begin to be
screened in individual cells.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Mechanisms in primary nociceptors that drive ongoing activity and ongoing pain
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批准号:10381714
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项目类别:
-
资助金额:$42.3万
-
财政年份:2019
-
负责人:EDGAR T. WALTERS
-
依托单位:
Mechanisms in Primary Nociceptors that Drive Ongoing Activity and Ongoing Pain
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批准号:10611897
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项目类别:
-
资助金额:$42.3万
-
财政年份:2019
-
负责人:EDGAR T. WALTERS
-
依托单位:
Mechanisms in primary nociceptors that drive ongoing activity and ongoing pain
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批准号:9908192
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项目类别:
-
资助金额:$42.08万
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财政年份:2019
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负责人:EDGAR T. WALTERS
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依托单位:
Sensory Plasticity During Central Neuropathic Pain Caused by Spinal Cord Injury
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批准号:7765622
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项目类别:
-
资助金额:$19.57万
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财政年份:2009
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负责人:EDGAR T. WALTERS
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依托单位:
NOCICEPTIVE MEMORY: MECHANISMS OF HYPEREXCITABILITY
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批准号:6193801
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项目类别:
-
资助金额:$34.31万
-
财政年份:1997
-
负责人:EDGAR T. WALTERS
-
依托单位:
PRIMITIVE FOUNDATIONS OF NEUROPATHIC HYPERALGESIA
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批准号:2703127
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项目类别:
-
资助金额:$16.28万
-
财政年份:1997
-
负责人:EDGAR T. WALTERS
-
依托单位:
Nociceptive Memory: Mechanisms of Hyperexcitability
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批准号:7017819
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项目类别:
-
资助金额:$33.41万
-
财政年份:1997
-
负责人:EDGAR T. WALTERS
-
依托单位:
NOCICEPTIVE MEMORY: MECHANISMS OF HYPEREXCITABILITY
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批准号:6639520
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项目类别:
-
资助金额:$33.52万
-
财政年份:1997
-
负责人:EDGAR T. WALTERS
-
依托单位:
Nociceptive Memory: Mechanisms of Hyperexcitability
-
批准号:7231967
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项目类别:
-
资助金额:$32.44万
-
财政年份:1997
-
负责人:EDGAR T. WALTERS
-
依托单位:
Nociceptive Memory: Mechanisms of Hyperexcitability
-
批准号:7417933
-
项目类别:
-
资助金额:$32.44万
-
财政年份:1997
-
负责人:EDGAR T. WALTERS
-
依托单位:
Nociceptive Memory: Mechanisms of Hyperexcitability
-
批准号:6922654
-
项目类别:
-
资助金额:$32.0万
-
财政年份:1997
-
负责人:EDGAR T. WALTERS
-
依托单位:
NOCICEPTIVE MEMORY: MECHANISMS OF HYPEREXCITABILITY
-
批准号:6726020
-
项目类别:
-
资助金额:$33.49万
-
财政年份:1997
-
负责人:EDGAR T. WALTERS
-
依托单位:
NOCICEPTIVE MEMORY: MECHANISMS OF HYPEREXCITABILITY
-
批准号:6393858
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项目类别:
-
资助金额:$33.32万
-
财政年份:1997
-
负责人:EDGAR T. WALTERS
-
依托单位:
NOCICEPTIVE MEMORY: MECHANISMS OF HYPEREXCITABILITY
-
批准号:6539914
-
项目类别:
-
资助金额:$33.6万
-
财政年份:1997
-
负责人:EDGAR T. WALTERS
-
依托单位:
PRIMITIVE FOUNDATIONS OF NEUROPATHIC HYPERALGESIA
-
批准号:2892197
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项目类别:
-
资助金额:$16.76万
-
财政年份:1997
-
负责人:EDGAR T. WALTERS
-
依托单位:
Nociceptive Memory: Mechanisms of Hyperexcitability
-
批准号:7613340
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项目类别:
-
资助金额:$32.44万
-
财政年份:1997
-
负责人:EDGAR T. WALTERS
-
依托单位:
ASSOCIATIVE INFORMATION PROCESSING: CELLULAR MECHANISMS
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批准号:3376838
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项目类别:
-
资助金额:$9.91万
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财政年份:1987
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负责人:EDGAR T. WALTERS
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依托单位:
ASSOCIATIVE INFORMATION PROCESSING: CELLULAR MECHANISMS
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批准号:3376839
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项目类别:
-
资助金额:$9.4万
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财政年份:1987
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负责人:EDGAR T. WALTERS
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依托单位:
ASSOCIATIVE INFORMATION PROCESSING CELLULAR MECHANISMS
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批准号:3376841
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项目类别:
-
资助金额:$12.79万
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财政年份:1987
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负责人:EDGAR T. WALTERS
-
依托单位:
ASSOCIATIVE INFORMATION PROCESSING CELLULAR MECHANISMS
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批准号:3376840
-
项目类别:
-
资助金额:$13.57万
-
财政年份:1987
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负责人:EDGAR T. WALTERS
-
依托单位:
海外基金