Progression of Headache Associated with Recurrent Dural Inflammation (PI: Michael
与复发性硬脑膜炎症相关的头痛的进展(PI:Michael
基本信息
- 批准号:8134800
- 负责人:
- 金额:$ 33.12万
- 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:2007-09-30 至 2013-08-31
- 项目状态:已结题
- 来源:
- 关键词:AccountingAcuteAffectAreaBrainCellsChemicalsChronicChronic Daily HeadachesChronic HeadachesClinicClinicalDiseaseDura MaterElectrophysiology (science)FrequenciesGeneral PopulationHeadacheHyperalgesiaInflammationInflammation MediatorsInflammatoryInfusion proceduresLeadMaintenanceMediator of activation proteinMedicalMicrodialysisMigraineModelingNeurogenic InflammationNeuronal PlasticityNeuronsNociceptorsPainPain-FreePatientsPerceptionPeripheralPharmaceutical PreparationsPharmacological TreatmentPhasePhysiciansPhysiologic MonitoringPhysiologicalPreventiveRattusRecording of previous eventsRecurrenceReportingRisk FactorsSensory ProcessSensory ThresholdsStimulusSystemTestingTimeTrigeminal NeuralgiaTrigeminal NucleiTrigeminal SystemVisitallodyniaawakeexperiencenervous system disorderneurochemistryneuromechanismpreventresearch studyresponsetheoriestreatment strategy
项目摘要
DESCRIPTION (provided by applicant):
Chronic daily headache (CDH) is a neurological disorder characterized by >15 headache days per month and affects up to 4% of the general population. Most cases of CDH evolve from episodic headache. CDH patients often report chronic pericranial tenderness (allodynia) with episodes of increased headache pain. Both a long history of headache and a high frequency of headache attacks are risk factors for the progression of episodic to chronic headache. Little is known about the physiological mechanism for the transition from episodic headache to CDH. One theory is that the pain phase of migraine involves nociceptor activation on the dura due to neurogenic inflammation. According to this theory, recurrent headache patients experience repeated attacks of inflammation and nociceptor activation on the dura over time. The overall aim of this study is to assess the mechanism of the progression of episodic to chronic headache following repeated dural inflammation. Studies show that repeated nociceptor activation produces long-lasting changes in the peripheral trigeminal neurons and their central projections in the brain. This can increase the perception of pain in secondary or referred areas due to activity-dependent neuronal plasticity. We have developed a model of recurrent headache in rat where we can induce inflammatory stimulation on the dura at fixed intervals over weeks. Repeated, episodic infusion of inflammatory soup (IS) on the dura of rats models the episodic activation of the dura in patients with recurrent headache. We propose to investigate the electrophysiological and neurochemical factors important for the progression of episodic to chronic trigeminal pain using this model. We hypothesize that repeated inflammatory stimulation of the dura induces chronic long lasting changes in trigeminal sensory processing in our rat model of CDH. In order to test this hypothesis, we propose 3 specific aims. Aim 1 will test the hypothesis that there is a critical frequency of inflammatory stimulation of the dura that causes the transition to low trigeminal thresholds. Aim 2 will test the hypothesis that the transition to chronically low trigeminal thresholds induces a long lasting hyperresponsive state of the electrophysiological and neurochemical responses in the trigeminal nucleus caudalis. Aim 3 will test the hypothesis that clinical headache treatment strategies, that effectively block allodynia and sensitization in patients, with block the transition of rats from episodic to chronic trigeminal pain following recurrent inflammatory stimulation of the dura. Project Narrative Recurrent headache is the most common pain-related complaint and the seventh leading ailment seen in medical practice, accounting for 18 million physician visits each year. Chronic daily headache is a disorder that affects up to 4% of the general population. The overall aim of this study is to assess the mechanism of the progression of episodic to chronic headache following repeated dural inflammation.
描述(由申请人提供):
慢性日常头痛 (CDH) 是一种神经系统疾病,其特征是每月头痛天数 >15 天,影响高达 4% 的总人口。大多数 CDH 病例都是由阵发性头痛演变而来。 CDH 患者经常报告慢性颅周压痛(异常性疼痛),并伴有头痛发作。头痛病史长和头痛发作频率高都是阵发性头痛进展为慢性头痛的危险因素。关于从阵发性头痛转变为 CDH 的生理机制知之甚少。一种理论认为,偏头痛的疼痛阶段涉及由于神经源性炎症而导致硬脑膜上的伤害感受器激活。根据这一理论,随着时间的推移,复发性头痛患者会经历反复发作的炎症和硬脑膜上伤害感受器的激活。本研究的总体目的是评估反复硬脑膜炎症后发作性头痛进展为慢性头痛的机制。研究表明,伤害感受器的反复激活会导致周围三叉神经元及其在大脑中的中央投射产生持久的变化。由于活动依赖性神经元可塑性,这可以增加次要区域或相关区域的疼痛感知。我们开发了一种大鼠复发性头痛模型,可以在几周内以固定的时间间隔诱导硬脑膜炎症刺激。在大鼠硬脑膜上反复、间歇性输注炎性汤(IS),模拟复发性头痛患者硬脑膜的间歇性激活。我们建议使用该模型研究对于阵发性三叉神经痛进展为慢性三叉神经痛重要的电生理学和神经化学因素。我们假设,在我们的 CDH 大鼠模型中,硬脑膜的反复炎症刺激会引起三叉神经感觉处理的慢性长期变化。为了检验这一假设,我们提出了 3 个具体目标。目标 1 将检验以下假设:硬脑膜炎症刺激存在临界频率,会导致向低三叉神经阈值的转变。目标 2 将检验这样的假设:向长期较低的三叉神经阈值的转变会引起三叉神经尾核电生理和神经化学反应的长期持续高反应状态。目标 3 将检验以下假设:临床头痛治疗策略可有效阻止患者的异常性疼痛和敏化,并阻止大鼠在硬脑膜反复炎症刺激后从阵发性三叉神经痛转变为慢性三叉神经痛。 项目叙述 复发性头痛是最常见的疼痛相关主诉,也是医疗实践中第七大疾病,每年导致 1800 万人次就诊。慢性每日头痛是一种影响高达 4% 人口的疾病。本研究的总体目的是评估反复硬脑膜炎症后发作性头痛进展为慢性头痛的机制。
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Pain remapping in migraine: a novel characteristic following trigeminal nerve injury.
偏头痛的疼痛重新映射:三叉神经损伤后的一个新特征。
- DOI:10.1111/j.1526-4610.2009.01436.x
- 发表时间:2010
- 期刊:
- 影响因子:5
- 作者:Hussain,Aamir;Stiles,MarlindA;Oshinsky,MichaelL
- 通讯作者:Oshinsky,MichaelL
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Michael L. Oshinsky其他文献
Michael L. Oshinsky的其他文献
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{{ truncateString('Michael L. Oshinsky', 18)}}的其他基金
Progression of Headache Associated with Recurrent Dural Inflammation (PI: Michael
与复发性硬脑膜炎症相关的头痛的进展(PI:Michael
- 批准号:
7686703 - 财政年份:2007
- 资助金额:
$ 33.12万 - 项目类别:
Progression of Headache Associated with Recurrent Dural Inflammation (PI: Michael
与复发性硬脑膜炎症相关的头痛的进展(PI:Michael
- 批准号:
7922521 - 财政年份:2007
- 资助金额:
$ 33.12万 - 项目类别:
Progression of Headache Associated with Recurrent Dural Inflammation (PI: Michael
与复发性硬脑膜炎症相关的头痛的进展(PI:Michael
- 批准号:
7502606 - 财政年份:2007
- 资助金额:
$ 33.12万 - 项目类别:
Progression of Headache Associated with Recurrent Dural Inflammation (PI: Michael
与复发性硬脑膜炎症相关的头痛的进展(PI:Michael
- 批准号:
7408415 - 财政年份:2007
- 资助金额:
$ 33.12万 - 项目类别:
VENTRAL FOREBRAIN NOREPINEPHRINE AND OPIATE WITHDRAWAL
腹侧前脑去甲肾上腺素和阿片戒断
- 批准号:
6055784 - 财政年份:1999
- 资助金额:
$ 33.12万 - 项目类别:
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