Pathophysiology of Occipital Migraine

枕叶偏头痛的病理生理学

基本信息

批准号：
10297828
负责人：
Rodrigo Noseda
金额：
$ 38.28万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-12-01 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10297828
关键词：
Acute Affect Anatomy Animals Anterior Applications Grants Auras Axon Back Bilateral Brain Stem Cell Nucleus Cells Cerebellar Diseases Cerebellum Cervical Manipulation Chemical Stimulation Clinical Complex Cutaneous Dendrites Dizziness Dura Mater Ear Electric Stimulation Endocrine Event Face Fiber Functional disorder Head Headache Hypothalamic structure Individual Label Lateral Lead Light Maps Mechanical Stimulation Mediating Migraine Motion Motor Muscle Myalgia Neck Nerve Neurons Neuropeptides Neurotransmitters Nociception Nociceptors Nucleus solitarius Oxytocin Pain Pathologic Pathway interactions Patients Pattern Periorbital Headaches Peripheral Physiological Play Posterior Horn Cells Process Property Reticular Formation Role Sensory Sensory Ganglia Sensory Process Serotonin Signal Transduction Sinus Site Skeletal muscle structure of neck Skin Symptoms Testing Thalamic Nuclei Therapeutic Tissues Travel Vertigo Visual Walking diencephalon dorsal horn experience experimental study hypocretin locus ceruleus structure migraine treatment nerve supply noradrenergic novel receptive field relating to nervous system spreading depression virtual

项目摘要

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.

项目摘要。枕部头痛可以是偏头痛或非偏头痛。经常先于或伴有头晕、眩晕、运动协调性下降、不稳定、不安全感行走、笨拙和协调性下降——所有这些都可以（至少部分）归因于小脑功能障碍 - 以及颈部运动加剧的肌肉压痛这两种情况表明。枕叶头痛可由颅内小脑功能异常的短暂发作引起，和/或颅外，由于颈部肌肉急性发作，超过 2/3 的偏头痛。患者会经历肌肉压痛，并辐射至后脑勺，但令人惊讶的是，人们对此知之甚少关于处理来自硬脑膜的伤害性信息的中枢神经元的功能特性覆盖小脑，更重要的是，人们对头痛的机制知之甚少起源于颅内的影响肌肉的感觉处理，反之亦然，颈部压痛如何肌肉影响来自后硬脑膜的感觉信号的处理。该提案的主要目标是。定义枕叶头痛的神经基础我们的工作假设是枕叶头痛可能颅内由小脑扩散性抑制（CbSD）引发，颅外由急性肌肉疼痛引发 – 每一种都涉及支配 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）产生偏头痛的一些典型症状并（b）调节放电该工作假设将在 3 个目标中进行测试：1）确定 CbSD 是否是能够激活和/或敏化 C2-4 背角神经元，这些神经元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源自小脑硬脑膜的感觉信号的程度；3）绘制这些神经元的轴突走向和投射目标，并确定它们是否接收来自下丘脑（即食欲素、催产素）、脑干（即 5HT）和感觉神经节（即 CGRP）神经元被认为在临床上，拟议的动物研究有可能产生新的结果。了解始于颅周组织的枕叶头痛与始于颅周组织的枕叶头痛有何不同在颅内治疗方面，这些发现可能会扩大我们对颈椎手术的理解。用于治疗偏头痛和非偏头痛；假设它是通过减少介导的；沿枕神经传播的伤害性信号包括减少伤害性信号从科学上讲，有可能确定疼痛纤维激活的新原因。后硬脑膜和处理此类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及其起源是否与额/眶周头痛不同。