TRIGEMINAL MECHANISMS OF VASCULAR HEAD PAIN

偏头痛以及其他形式的血管性头痛是其中最 常见的医疗问题。 通常，它与重大变化有关 在情感和生理功能上。 它是一种 严重的头痛和这些变化带来的痛苦和损害 生活品质 尽管事实上，痛苦产生于深 结构（如颅内血管）通常具有更大的 临床重要性高于皮肤器官引起的疼痛（如 皮肤），大多数疼痛研究集中在皮肤疼痛上。 因此，在本发明中， 偏头痛、血管性头痛和其他头痛的神经基础是 人们对此知之甚少，争议很大，因此没有得到治疗。 适当地。 早期的研究表明，偏头痛和血管 头痛可能是通过疼痛敏感纤维，分支的 三叉神经，支配颅血管。 但由于 存在关于所述细胞的基本生理特性的最少信息。 颅血管感觉通路，对它的了解极为有限。 为了更好地了解这种感觉通路，我们最近 识别外周（15个单位）和中央（10个单位）三叉神经元 它们支配静脉窦，记录它们对电流的反应， 机械和化学刺激，监测其 活动，并将他们的一些轴突投射映射到更高的大脑 地区 拟议中的实验将通过以下方式增进我们的知识： 调查检测和传播的生理基础， 起源于颅血管的伤害性（疼痛）信号。 在 第一项研究，我们将继续从生理学上描述 初级传入神经元，通过以下方式支配硬脑膜和窦 在三叉神经节中的单个神经元的细胞外记录。 在第二项研究中，我们将确定潜在的 使化学刺激对自发活动和敏感性敏感， 这些硬脑膜反应的初级传入神经元，通过施加炎性 介导剂到硬脑膜。 在第三项研究中，我们将继续 三叉神经的二级神经元的生理特征 支配硬脑膜和鼻窦的脑干核团，决定着 炎症介质的活性，并确定其投影 大脑中的目标。 在第四项研究中，我们将确定 通过测量伤害性硬脑膜刺激后大脑活动增加 2-脱氧葡萄糖，c-fos和碘安替比林。 这些研究将提供 关于能够激活神经元的刺激种类的信息 颅血管感觉通路，外周和中枢的作用 维持血管性头痛的敏感性， 这些脑血管信息，以及哪些大脑区域 参与了血管性头痛的过程。 这些研究一起 对于进一步理解脑电的神经基础至关重要， 血管性头痛

Migraine as well as other forms of vascular headache is among the most common of medical problems. Usually, it is associated with major changes in emotional and physiological functions. And it is the combination of the severe head pain and these changes that bring about suffering and impair the quality of life. In spite of the fact that pain that arises from deep structures (such as intracranial blood vessels) is generally of greater clinical importance than pain that arises from cutaneous organs (such as the skin), most pain research has focused on cutaneous pain. As a result, the neural basis of migraine, vascular headache and other head pains is poorly understood and highly controversial, and therefore not treated appropriately. Earlier studies suggested that migraine and vascular headache may be mediated through pain-sensitive fibers, branches of the trigeminal nerve, that innervate cranial blood vessels. However, because minimal information exists about the basic physiological properties of the craniovascular sensory pathway, understanding of it is extremely limited. To gain a better understanding of this sensory pathway we have recently identified peripheral (15 units) and central (10 units) trigeminal neurons that innervate the venous sinuses, recorded their responses to electrical, mechanical and chemical stimulation, monitored lasting changes in their activity, and mapped some of their axonal projections to higher brain regions. The proposed experiments will further our knowledge by investigating the physiological basis for the detection and transmission of nociceptive (painful) signals that originate in cranial blood vessels. In the first study we will continue to physiologically characterize athe primary afferent neurons that innervate the dura and sinuses by extracellularly recording from single neurons in the trigeminal ganglion. In the second study we will determine the effects of potentially sensitizing chemical stimuli on the spontaneous activity and sensitivity of these dura responsive primary afferent neurons by applying inflammatory mediators to the dura. In the third study we will continue to physiologically characterize the second order neurons in the trigeminal brainstem nuclei that innervate the dura and sinuses, determine the effects of inflammatory mediators on their activity, and identify their projection targets in the brain. In the fourth study we will identify areas of increased brain activity following noxious dural stimulation by measuring 2-deoxyglucose, c-fos and iodoantipyrine. These studies will provide information about the kinds of stimuli capable of activating athe craniovascular sensory pathway, the role of peripheral and central sensitization in maintaining vascular headache, which brain areas receive this craniovascular information directly, and which brain areas are involved in the processing of vascular head pain. Together, these studies are critical for further progress in understanding the neural basis of vascular head pain.