Cortical Mechanisms of Headache: Beyond CSD

头痛的皮质机制:超越 CSD

基本信息

  • 批准号:
    9898471
  • 负责人:
  • 金额:
    $ 37.84万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-07-01 至 2023-02-28
  • 项目状态:
    已结题

项目摘要

Project Summary A large body of indirect evidence now strongly supports the idea that the nociceptive sensory pathway that innervates the intracranial meninges (the trigeminovascular system) is involved in the generation of some types of clinically occurring headaches, including migraine. The basic properties of this sensory pathway have been studied in detail in animal studies, but it is not yet well understood how this pathway becomes activated during a clinically occurring headache attack. One leading line of research has provided evidence in support of the CSD (cortical spreading depression) theory of migraine, including the recent findings of trigeminovascular neuron activation following CSD induction in animals. However, the study of CSD in migraine patients is necessarily somewhat anecdotal because CSD cannot be detected by routine methods in humans, and so it is not known how often it occurs, or what causes it to arise spontaneously. As a new avenue to further explore the mechanisms that can trigger headache and the potential role of cortical pathophysiology, we now propose to examine mechanisms of trigeminovascular neuron activation in an animal model of a common type of cortical pathophysiology that is well described and intensively studied in humans: cortical seizure. Based on the clinical observation that seizures are commonly followed by headache with features similar to migraine, we hypothesize that seizure can produce activation of the trigeminovascular system. We therefore propose to test this hypothesis, and to use seizure as a model to further investigate the mechanisms by which cortical processes can influence the trigeminovascular system, in the following Aims: (1) Employing single-unit recording to monitor changes in activity of first-order dura-sensitive neurons in the trigeminal ganglion, we will test the hypothesis that chemically-induced seizures can induce activation and/or sensitization of dural nociceptors. Seizure-induced effects will also be examined in trigeminal ganglion neurons that do not innervate the dura. (2) Using single-unit recording, changes in activity of second-order dural-responsive neurons in the superficial and deep laminae of the upper cervical and medullary dorsal horn will be examined following seizures in anesthetized rats. As in Aim 1, neurons that lack a dural response will also be studied. Data analysis will determine the latency, duration, and magnitude of changes in activity induced by seizure, and compare the seizure effects in dura-sensitive vs. dura-insensitive neurons. Experiments will test the hypothesis that neuronal activation will be produced by focal seizure in occipital but not parietal cortical sites, paralleling the regionally selective pattern found for the occurrence of postictal headache. In order to determine whether the seizure-induced discharge originates in terminals within the dural receptive field, lidocaine will be applied to the dura either prior to seizure induction or following seizure induction during the period of peak seizure- induced discharge.
项目摘要 大量的间接证据现在强烈支持这样的观点,即伤害性感觉通路, 神经支配颅内脑膜(三叉神经血管系统)参与产生一些 包括偏头痛在内的临床头痛类型。这种感觉通路的基本特性有 在动物研究中已经详细研究过,但还没有很好地了解这种途径是如何被激活的 在临床上出现的头痛发作。一项主要的研究提供了证据,支持 偏头痛的CSD(皮质扩散性抑制)理论,包括三叉神经血管的最新发现 在动物中CSD诱导后的神经元活化。然而,偏头痛患者的CSD研究是 因为CSD不能通过常规方法在人类中检测到,所以它是 不知道它多久发生一次,也不知道是什么原因导致它自发出现。作为进一步探索的新途径 引发头痛的机制和皮质病理生理学的潜在作用,我们现在提出 研究三叉神经血管神经元激活的机制,在动物模型中的一种常见类型的 在人类中被充分描述和深入研究的皮质病理生理学:皮质癫痫发作。基于 临床观察发现癫痫发作后常伴有类似偏头痛的头痛, 假设癫痫发作可引起三叉神经血管系统激活。因此,我们建议测试 这一假设,并使用癫痫发作作为模型,以进一步研究的机制,皮层 过程可以影响三叉神经血管系统,在以下目的:(1)采用单单位 记录监测三叉神经节中一级硬膜敏感神经元的活动变化,我们将 测试化学诱导的癫痫发作可以诱导硬脑膜激活和/或致敏的假设 伤害感受器还将在不受神经支配的三叉神经节神经元中检查癫痫发作诱导的效应 硬脑膜(2)用单单位记录方法,观察了海马背外侧核二级反应神经元活动的变化, 检查上颈和髓背角的浅层和深层, 麻醉大鼠的癫痫发作。与目标1一样,也将研究缺乏硬脑膜反应的神经元。数据 分析将确定癫痫发作引起的活动变化的潜伏期、持续时间和幅度, 比较硬脑膜敏感神经元与硬脑膜不敏感神经元的癫痫发作效应。实验将检验这一假设 枕叶皮质部位的局灶性癫痫发作会产生神经元激活,而顶叶皮质部位则不会,与之平行 发作后头痛发生的区域选择性模式。为了确定是否 麻醉诱导的放电起源于硬脑膜感受野内的末梢,利多卡因将被应用于 在癫痫发作诱导之前或癫痫发作诱导之后的癫痫发作高峰期期间的硬脑膜- 诱发放电

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Rami Burstein其他文献

Rami Burstein的其他文献

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{{ truncateString('Rami Burstein', 18)}}的其他基金

Narrow band green light effects on cortical excitability and responsivity in migraine
窄带绿光对偏头痛皮质兴奋性和反应性的影响
  • 批准号:
    10675293
  • 财政年份:
    2023
  • 资助金额:
    $ 37.84万
  • 项目类别:
Cortical Mechanisms of Headache: Beyond CSD
头痛的皮质机制:超越 CSD
  • 批准号:
    9276807
  • 财政年份:
    2016
  • 资助金额:
    $ 37.84万
  • 项目类别:
Photophobia during migraine: sensory, autonomic and emotional responses to light
偏头痛期间的畏光:对光的感觉、自主和情绪反应
  • 批准号:
    8694112
  • 财政年份:
    2012
  • 资助金额:
    $ 37.84万
  • 项目类别:
Photophobia during migraine: sensory, autonomic and emotional responses to light
偏头痛期间的畏光:对光的感觉、自主和情绪反应
  • 批准号:
    8925932
  • 财政年份:
    2012
  • 资助金额:
    $ 37.84万
  • 项目类别:
Photophobia during migraine: sensory, autonomic and emotional responses to light
偏头痛期间的畏光:对光的感觉、自主和情绪反应
  • 批准号:
    8343319
  • 财政年份:
    2012
  • 资助金额:
    $ 37.84万
  • 项目类别:
Photophobia during migraine: sensory, autonomic and emotional responses to light
偏头痛期间的畏光:对光的感觉、自主和情绪反应
  • 批准号:
    8499450
  • 财政年份:
    2012
  • 资助金额:
    $ 37.84万
  • 项目类别:
Migraine pathophysiology: neural basis of photophobia
偏头痛病理生理学:畏光的神经基础
  • 批准号:
    8299868
  • 财政年份:
    2010
  • 资助金额:
    $ 37.84万
  • 项目类别:
Migraine pathophysiology: neural basis of photophobia
偏头痛病理生理学:畏光的神经基础
  • 批准号:
    7863432
  • 财政年份:
    2010
  • 资助金额:
    $ 37.84万
  • 项目类别:
Migraine pathophysiology: neural basis of photophobia
偏头痛病理生理学:畏光的神经基础
  • 批准号:
    8606265
  • 财政年份:
    2010
  • 资助金额:
    $ 37.84万
  • 项目类别:
Migraine pathophysiology: neural basis of photophobia
偏头痛病理生理学:畏光的神经基础
  • 批准号:
    8013547
  • 财政年份:
    2010
  • 资助金额:
    $ 37.84万
  • 项目类别:

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