Pathophysiology of Occipital Migraine

项目摘要。枕骨头痛可以是偏头痛或非偏头痛。当偏头痛时， 常伴有头晕、眩晕、运动协调性下降、不稳定、不安全 行走、笨拙和协调能力下降-所有这些都可以归因于（至少部分）小脑 功能障碍-和肌肉压痛，颈部运动加重。这两种情况表明， 枕叶头痛可由颅内触发，由小脑功能异常的短暂发作， 和/或通过颈部肌肉疼痛的急性发作在颅外。鉴于超过2/3的偏头痛 患者会经历放射到后脑勺的肌肉压痛，令人惊讶的是， 关于处理硬脑膜伤害性信息的中枢神经元的功能特性 覆盖在小脑上，更重要的是，对头痛的机制知之甚少。 起源于颅内影响肌肉的感觉处理，反之亦然， 肌肉影响来自硬脑膜后部的感觉信号的处理。这项建议的主要目标是 来确定枕部头痛的神经基础我们的假设是枕部头痛 由小脑扩散性抑制（CbSD）在颅内和急性肌肉疼痛在颅外引发- 每一个都涉及不同的C2-4背角神经元的激活和敏化模式， 后硬脑膜和颈肌，其轴突与脑干建立相互联系， 下丘脑核团，其（a）产生偏头痛的一些经典症状和（B）调节放电 同样的神经元。这一工作假设将在3个目标进行测试：1）确定CbSD是否是 能够激活和/或敏化C2-4背角神经元，其接收来自 枕骨硬脑膜和颈部肌肉; 2）确定肌肉疼痛的诱导是否可以使这些神经元敏感， 它影响它们如何处理起源于小脑硬脑膜的感觉信号的程度;以及3）映射 这些神经元的轴突路线和投射目标，并确定它们是否接受来自 下丘脑（即食欲素，催产素），脑干（即，5 HT）和感觉神经节（即CGRP）神经元被认为是 在偏头痛的病理生理学中起作用。临床上，拟议的动物研究有可能产生新的 关于开始于颅周组织的枕头痛与开始的枕头痛有何不同 颅内在治疗上，这些发现可能会扩大我们对颈椎手法的理解， 用于治疗偏头痛和非偏头痛;从假设它是由减少介导 伤害感受信号沿枕神经沿着传播的减少，包括伤害感受信号的减少， 起源于硬脑膜后部科学家们认为，有可能确定新的原因激活疼痛纤维， 后硬脑膜和处理这种疼痛的中枢网络可以更深入地了解 枕部头痛的病理生理学以及其起源是否与额叶/眶周头痛不同。

Project Summary. Occipital headaches can be migrainous or non-migraineous. When migrainous, they are often preceded or accompanied by dizziness, vertigo, decreased motor coordination, instability, insecure walking, clumsiness, and reduced coordination – all of which could be attributed (at least partially) to cerebellar dysfunction – and muscle tenderness that is aggravated by neck motion. These 2 scenarios suggest that occipital headache can be triggered intracranially, by transient episodes of abnormal cerebellar functioning, and/or extracranially, by acute episodes of neck muscles ache. Given that more than 2/3 of all migraine patients experience muscle tenderness that radiates to the back of the head, it is surprising how little is known about the functional properties of the central neurons that process nociceptive information from the dura overlying the cerebellum, and even more so, how little is known about the mechanisms by which headaches that originate intracranially affect sensory processing of muscles and, vice versa, how tenderness of neck muscles affects processing of sensory signals from the posterior dura. The broad objective of this proposal is to define the neural substrate of occipital headaches. Our working hypothesis is that occipital headaches could be initiated intracranially by cerebellar spreading depression (CbSD) and extracranially by acute muscle pain – each one involving different patterns of activation and sensitization of C2-4 dorsal horn neurons that innervate posterior dura and neck muscles, and whose axons establish reciprocal connections with brainstem and hypothalamic nuclei that (a) generate some of the classical symptoms of migraine and (b) modulate the firing of these same neurons. This working hypothesis will be tested in 3 aims: 1) determine whether CbSD is capable of activating and/or sensitizing C2-4 dorsal horn neurons that receive convergent signals from the occipital dura and neck muscles; 2) determine whether induction of muscle pain can sensitize these neurons to the extent that it affects how they process sensory signals that originate in the cerebellar dura; and 3) map the axonal course and projection targets of these neurons, and determine whether they receive input from hypothalamic (i.e. orexin, oxytocin), brainstem (i.e., 5HT) and sensory ganglia (i.e. CGRP) neurons thought to play a role in migraine pathophysiology. Clinically, the proposed animal studies have the potential to shed new light on how occipital headaches that begin in pericranial tissues differ from occipital headaches that begin intracranially. Therapeutically, the findings may expand our understanding of cervical manipulations commonly used in the treatment of migraine and non-migraine headaches; from assuming that it is mediated by reduction of nociceptive signals travelling along the occipital nerve to include reduction of nociceptive signals that originate in the posterior dura. Scientifically, the potential to identify novel causes of activation of pain fibers in the posterior dura and the central networks that process such pain can lead to a deeper understanding of the pathophysiology of occipital headache and whether its origin differs from that of frontal/periorbital headache.