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
• 负责人: Michael L. Oshinsky
• 金额: $ 33.8万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7502606
• 关键词: Accounting; Acute; Affect; Area; Brain; Cells; Chemicals; Chronic; Chronic Daily Headaches; Chronic Headaches; Clinic; Clinical; Daily; Disease; Dura Mater; Electrophysiology (science); Frequencies; General Population; Headache; Hyperalgesia; Inflammation; Inflammatory; Infusion procedures; Lead; Maintenance; Mediator of activation protein; Medical; Microdialysis; Migraine; Modeling; Neurogenic Inflammation; Neuronal Plasticity; Neurons; Nociceptors; Numbers; Pain; Pain-Free; Patients; Perception; Peripheral; Pharmaceutical Preparations; Pharmacological Treatment; Phase; Physicians; Physiologic Monitoring; Physiological; Preventive; Rattus; Recording of previous events; Recurrence; Reporting; Risk Factors; Sensory Process; Sensory Thresholds; Stimulus; System; Testing; Time; Trigeminal Neuralgia; Trigeminal Nuclei; Trigeminal System; Visit; Week; allodynia; awake; day; experience; nervous system disorder; neurochemistry; neuromechanism; prevent; research study; response; theories

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）： 慢性每日头痛（CDH）是一种神经系统疾病，其特征是每月> 15个头痛日，影响高达4%的一般人群。大多数CDH病例由发作性头痛演变而来。CDH患者经常报告慢性颅周压痛（异常性疼痛）伴头痛发作增加。长期头痛史和高频率头痛发作都是发作性头痛进展为慢性头痛的危险因素。关于从发作性头痛向CDH转变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引起的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硬膜上反复的炎症和伤害性感受器激活。本研究的总体目的是评估反复硬膜炎症后发作性头痛进展为慢性头痛的机制。研究表明，重复的伤害感受器激活会在外周三叉神经元及其在大脑中的中枢投射中产生持久的变化。由于活动依赖性神经元可塑性，这可以增加次级或涉及区域的疼痛感知。我们已经开发了一种大鼠复发性头痛模型，在该模型中，我们可以在数周内以固定的间隔在硬脑膜上诱导炎症刺激。在大鼠硬脑膜上反复、间歇性地注入炎性汤（IS）可模拟复发性头痛患者硬脑膜的间歇性激活。我们建议调查的电生理和神经化学因素的重要进展，偶发性慢性三叉神经痛使用这个模型。我们假设，在我们的CDH大鼠模型中，硬脑膜的反复炎症刺激诱导三叉神经感觉处理的慢性持久变化。为了验证这一假设，我们提出了三个具体目标。目的1将检验以下假设：硬脑膜炎性刺激存在一个临界频率，导致三叉神经阈值降低。目的2将测试的假设，过渡到长期低三叉神经阈值诱导长期持续的高反应状态的电生理和神经化学反应的三叉神经核尾侧。目的3将检验以下假设：有效阻断患者的异常性疼痛和致敏的临床头痛治疗策略，阻断在硬脑膜的反复炎症刺激后大鼠从偶发性三叉神经痛向慢性三叉神经痛的转变。 复发性头痛是最常见的疼痛相关主诉，也是医疗实践中的第七大疾病，每年有1800万人次就诊。慢性每日头痛是一种影响高达4%的一般人群的疾病。本研究的总体目的是评估反复硬膜炎症后发作性头痛进展为慢性头痛的机制。