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
• 负责人: Michael L. Oshinsky
• 金额: $ 28.47万
• 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/7408415
• 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)是一种神经疾病，其特征是每月头痛15天，影响多达4%的普通人群。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(异常疼痛)，并伴有阵发性头痛。长期的头痛病史和高频率的头痛发作都是发作性头痛进展为慢性头痛的危险因素。发作性头痛转变为CDH的生理机制目前知之甚少。一种理论认为，偏头痛的痛相涉及神经源性炎症引起的硬脑膜伤害性感受器激活。根据这一理论，随着时间的推移，反复头痛的患者会经历炎症和硬脑膜伤害性感受器激活的反复发作。这项研究的总体目标是评估反复硬脑膜炎症后发作性头痛向慢性头痛发展的机制。研究表明，反复激活伤害性感受器会导致三叉神经外周神经元及其在大脑中的中枢投射产生长期的变化。由于依赖活动的神经元的可塑性，这可以增加次级或牵涉区的疼痛感知。我们已经建立了一种反复头痛的大鼠模型，在该模型中，我们可以在几周内以固定的间隔在硬脑膜上诱导炎症刺激。反复、间歇性地在大鼠硬脑膜上灌注炎性汤(IS)，以模拟反复头痛患者的间歇性硬脑膜激活。我们建议使用这个模型来研究三叉神经阵发性疼痛向慢性三叉神经痛发展的电生理和神经化学因素。我们假设，反复的硬脑膜炎症刺激导致CDH模型大鼠三叉神经感觉加工的慢性、持久的变化。为了验证这一假设，我们提出了三个具体目标。目的1将验证硬脑膜存在炎性刺激的临界频率导致向低三叉神经阈值过渡的假设。目的2验证三叉神经尾侧核电生理和神经化学反应的长期高反应状态的假说。目的3验证临床头痛治疗策略是否能有效阻断患者的异位痛觉和敏感化，并阻断大鼠在反复硬脑膜炎症刺激后从发作性三叉神经痛向慢性三叉神经痛的转变。项目叙述复发性头痛是最常见的疼痛相关主诉，也是医疗实践中看到的第七大疾病，每年有1800万名医生就诊。慢性日常头痛是一种影响高达4%的普通人群的疾病。这项研究的总体目标是评估反复硬脑膜炎症后发作性头痛向慢性头痛发展的机制。