Pathophysiology of Occipital Migraine

项目摘要。枕部头痛可以是偏头痛，也可以是非偏头痛。当偏头痛时，他们会 经常出现或伴随有眩晕、眩晕、运动协调性下降、不稳定、缺乏安全感 走路、笨拙和协调性降低--所有这些都可以(至少部分地)归因于小脑 功能障碍--颈部运动会加重肌肉压痛。这两种情况表明 枕部头痛可由短暂的小脑功能异常发作在脑内触发， 和/或颅外，由急性发作的颈部肌肉疼痛引起。鉴于超过2/3的偏头痛 患者的肌肉压痛辐射到脑后，令人惊讶的是，人们对此知之甚少。 关于处理硬脑膜伤害性信息的中枢神经元的功能特性 更重要的是，人们对头痛的机制知之甚少 它们起源于颅内，影响肌肉的感觉处理，反之亦然，颈部的压痛 肌肉影响来自后硬脑膜的感觉信号的处理。这项提议的总体目标是 以明确枕部头痛的神经基础。我们的工作假设是枕部头痛可能 由小脑弥漫性抑制(CBSD)在颅内启动，在颅外由急性肌肉疼痛启动- 每一个都涉及到支配C2-4背角神经元的不同激活和敏化模式 后硬脑膜和颈部肌肉，其轴突与脑干和 下丘脑核团，(A)产生一些典型的偏头痛症状，(B)调节放电 这些相同的神经元。这一工作假说将在3个目标中得到验证：1)确定CBSD是否 能够激活和/或敏化C2-4背角神经元，这些神经元从 枕部硬脑膜和颈部肌肉；2)确定肌肉疼痛的诱导是否能使这些神经元对 它影响他们如何处理源自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靶点，并确定它们是否接受来自 下丘脑(即食欲素、催产素)、脑干(即5HT)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发挥作用。在临床上，拟议的动物研究有可能带来新的 说明始于颅骨周围组织的枕部头痛与始于枕部的头痛有何不同 在脑内。在治疗上，这些发现通常可以扩大我们对颈椎手法的理解。 用于偏头痛和非偏头痛的治疗；从假设它是通过减少来调节的 伤害性信号沿枕神经传播，包括伤害性信号的减少， 起源于后硬脑膜。科学上，确定疼痛纤维激活的新原因的可能性 后硬脑膜和处理这种疼痛的中央网络可以使我们更深入地了解 枕部头痛的病理生理学以及其起源是否有别于额部/眶周头痛。

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.