Jacobs Blaine, Dussor Gregory
Behavioral and Brain Sciences, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080, United States.
Behavioral and Brain Sciences, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080, United States.
Neuroscience. 2016 Dec 3;338:130-144. doi: 10.1016/j.neuroscience.2016.06.012. Epub 2016 Jun 14.
Migraine is the third most common disease worldwide, the most common neurological disorder, and one of the most common pain conditions. Despite its prevalence, the basic physiology and underlying mechanisms contributing to the development of migraine are still poorly understood and development of new therapeutic targets is long overdue. Until recently, the major contributing pathophysiological event thought to initiate migraine was cerebral and meningeal arterial vasodilation. However, the role of vasodilation in migraine is unclear and recent findings challenge its necessity. While vasodilation itself may not contribute to migraine, it remains possible that vessels play a role in migraine pathophysiology in the absence of vasodilation. Blood vessels consist of a variety of cell types that both release and respond to numerous mediators including growth factors, cytokines, adenosine triphosphate (ATP), and nitric oxide (NO). Many of these mediators have actions on neurons that can contribute to migraine. Conversely, neurons release factors such as norepinephrine and calcitonin gene-related peptide (CGRP) that act on cells native to blood vessels. Both normal and pathological events occurring within and between vascular cells could thus mediate bi-directional communication between vessels and the nervous system, without the need for changes in vascular tone. This review will discuss the potential contribution of the vasculature, specifically endothelial cells, to current neuronal mechanisms hypothesized to play a role in migraine. Hypothalamic activity, cortical spreading depression (CSD), and dural afferent input from the cranial meninges will be reviewed with a focus on how these mechanisms can influence or be impacted by blood vessels. Together, the data discussed will provide a framework by which vessels can be viewed as important potential contributors to migraine pathophysiology, even in light of the current uncertainty over the role of vasodilation in this disorder.
偏头痛是全球第三大常见疾病，是最常见的神经系统疾病之一，也是最常见的疼痛病症之一。尽管其发病率很高，但导致偏头痛发生的基本生理学和潜在机制仍知之甚少，早就应该开发新的治疗靶点了。直到最近，人们认为引发偏头痛的主要病理生理事件是脑和脑膜动脉血管舒张。然而，血管舒张在偏头痛中的作用尚不清楚，最近的研究结果对其必要性提出了挑战。虽然血管舒张本身可能与偏头痛无关，但在没有血管舒张的情况下，血管仍有可能在偏头痛病理生理学中发挥作用。血管由多种细胞类型组成，这些细胞既释放又对多种介质作出反应，包括生长因子、细胞因子、三磷酸腺苷（ATP）和一氧化氮（NO）。这些介质中的许多对神经元有作用，可能导致偏头痛。相反，神经元释放诸如去甲肾上腺素和降钙素基因相关肽（CGRP）等因子，这些因子作用于血管原生细胞。因此，血管细胞内和细胞间发生的正常和病理事件都可以介导血管与神经系统之间的双向通信，而无需血管张力的变化。本综述将讨论脉管系统，特别是内皮细胞，对目前假设在偏头痛中起作用的神经元机制的潜在贡献。将对下丘脑活动、皮层扩散性抑制（CSD）和来自颅脑膜的硬脑膜传入输入进行综述，重点关注这些机制如何影响血管或受到血管的影响。总之，所讨论的数据将提供一个框架，据此即使鉴于目前血管舒张在这种疾病中的作用存在不确定性，血管也可被视为偏头痛病理生理学的重要潜在促成因素。
