Model of Chronic Daily Headache in Rat

大鼠慢性每日头痛模型

• 批准号: 7491444
• 负责人: Michael L. Oshinsky
• 金额: $ 16.95万
• 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: 2007-09-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7491444
• 关键词: Accounting; Acute; Affect; Afferent Neurons; Animal Model; Behavioral Model; Biological Models; Body Regions; Brain; Chronic; Chronic Daily Headaches; Clinical; Clinical Treatment; Consultations; Daily; Data; Development; Dura Mater; Electrophysiology (science); Exhibits; Exploratory/Developmental Grant; Face; Functional disorder; General Population; Headache; Headache Disorders; Hour; Human; Inflammation; Inflammatory; Infusion procedures; Measures; Medical; Migraine; Modeling; Monitor; Nitric Oxide; Nitric Oxide Donors; Nitroglycerin; Non-Steroidal Anti-Inflammatory Agents; Pain; Pain Disorder; Patients; Pharmaceutical Preparations; Physicians; Preventive; Rattus; Recurrence; Reporting; Research; Saline; Sensory Thresholds; Source; Study models; Superior sagittal sinus; Symptoms; Syndrome; System; Testing; Time; Trigeminal Neuralgia; Trigeminal Nuclei; Visit; Week; allodynia; awake; base; day; human study; neurochemistry; pressure; prophylactic; research study; response

DESCRIPTION (provided by applicant): 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 1. Recent evidence from a variety of sources indicates that inflammation of the dura is important for recurrent headache disorders. Chronic daily headache (CDH) is a pain disorder characterized by >15 headache days per month and affects up to 4% of the general population. Most cases of CDH evolve from episodic migraine. Little is known about how episodic migraine transforms into CDH, in part, because there are currently are no validated animal models to study the pathophysiology of CDH. In the preliminary data for this application, we report the development of a model of CDH using repeated application of inflammatory soup to the dura in awake, behaving rats. These data indicate that repetitive stimulation of the dura with an inflammatory soup (IS) leads to chronic pressure and brush allodynia in the periorbital region of the rat. Following the first few infusions of IS, changes in sensory thresholds resolve in hours. After multiple infusions, there is a chronic allodynic state that persists. In addition, in many of the rats, allodynia spreads to extracephalic regions of the body. Based on our preliminary findings, we propose the following 2 specific aims to test the hypothesis that repetitive infusion of IS on the dura is an accurate model for studying the pathophysiology of chronic daily headache. These aims will demonstrate that this system models CDH because it responds to proven clinical treatments of CDH in humans. Aim 1 will test the hypothesis that established preventive treatments for migraine in humans will block the transition of the rats from episodic to chronic trigeminal pain following repetitive IS infusion on the dura. Aim 2 will test the hypothesis that acute migraine treatments such as triptans are less effective in rats that have received chronic IS infusions.

描述（由申请人提供）：头痛是最常见的疼痛相关的投诉和第七大疾病在医疗实践中看到，占18万医生访问每年1。最近来自各种来源的证据表明，硬脑膜炎症是复发性头痛疾病的重要原因。慢性每日头痛（CDH）是一种疼痛障碍，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病例是由发作性偏头痛演变而来的。关于发作性偏头痛如何转变为CDH知之甚少，部分原因是目前没有有效的动物模型来研究CDH的病理生理学。在本申请的初步数据中，我们报告了CDH模型的开发，该模型使用在清醒的行为大鼠的硬脑膜中反复应用炎症汤。这些数据表明，反复刺激硬膜炎汤（IS）导致慢性压力和刷异常性疼痛的大鼠眶周区域。在最初几次注射IS后，感觉阈值的变化在数小时内消退。多次输注后，存在持续的慢性异常性疼痛状态。此外，在许多大鼠中，异常性疼痛扩散到身体的脑外区域。基于我们的初步研究结果，我们提出了以下2个具体的目的来检验这一假设，即在硬脑膜上重复输注IS是研究慢性每日头痛的病理生理学的准确模型。这些目标将证明该系统模拟CDH，因为它响应于人类CDH的经证实的临床治疗。目的1将检验以下假设：在硬脑膜上重复IS输注后，人类偏头痛的既定预防性治疗将阻断大鼠从偶发性三叉神经痛向慢性三叉神经痛的转变。目的2将测试急性偏头痛治疗如曲坦类药物在接受慢性IS输注的大鼠中效果较差的假设。

项目成果

Spontaneous trigeminal allodynia in rats: a model of primary headache.

• DOI: 10.1111/j.1526-4610.2012.02247.x
• 发表时间: 2012-10
• 期刊: Headache
• 影响因子: 5
• 作者: Oshinsky ML;Sanghvi MM;Maxwell CR;Gonzalez D;Spangenberg RJ;Cooper M;Silberstein SD
• 通讯作者: Silberstein SD

Is phonophobia associated with cutaneous allodynia in migraine?

• DOI: 10.1136/jnnp.2009.198481
• 发表时间: 2010-11-01
• 期刊: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
• 影响因子: 11
• 作者: Ashkenazi, Avi;Yang, Irene;Oshinsky, Michael L.
• 通讯作者: Oshinsky, Michael L.

Tension-type headache with medication overuse: pathophysiology and clinical implications.

过度使用药物引起的紧张型头痛：病理生理学和临床意义。

• DOI: 10.1007/s11916-009-0075-0
• 发表时间: 2009
• 期刊: Current pain and headache reports
• 影响因子: 3.7
• 作者: Monteith,TeshamaeS;Oshinsky,MichaelL
• 通讯作者: Oshinsky,MichaelL

Acetate causes alcohol hangover headache in rats.

• DOI: 10.1371/journal.pone.0015963
• 发表时间: 2010-12-31
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Maxwell CR;Spangenberg RJ;Hoek JB;Silberstein SD;Oshinsky ML
• 通讯作者: Oshinsky ML