Neural Basis of Occipital Headache

枕叶头痛的神经基础

• 批准号: 8969372
• 负责人: Rodrigo Noseda
• 金额: $ 26.1万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8969372
• 关键词: Affect; Anatomy; Animals; Anterior; Applications Grants; Area; Axon; Back; Blood Vessels; Cells; Cerebellum; Cervical; Cervicogenic Headaches; Chemical Stimulation; Classification; Cutaneous; Cutaneous Muscle; Dura Mater; Ear; Electric Stimulation; Esthesia; Event; Face; Foundations; Functional disorder; Future; Ganglia; Green Fluorescent Proteins; Head; Headache; Individual; Inflammation; Inflammatory; Label; Lead; Light; Maps; Mechanical Stimulation; Mediating; Meningeal; Migraine; Muscle; Muscle Cramp; Neck; Nerve; Neurons; Neurotransmitters; Nociception; Nociceptors; Occipital lobe; Pain; Patients; Periorbital Headaches; Peripheral; Physiological; Physiology; Plant Roots; Posterior Fossa; Posterior Horn Cells; Process; Property; Recombinant adeno-associated virus (rAAV); Reporter Genes; Sensory; Sensory Process; Shoulder; Signal Transduction; Sinus; Skeletal muscle structure of neck; Skin; Spasm; Superior sagittal sinus; Supratentorial; TRP channel; Techniques; Tension Headache; Testing; Tissues; Travel; Trigeminal System; Work; base; behavioral study; cranium; dorsal horn; experience; information processing; irritation; malformation; nerve supply; neuronal cell body; novel; occipital bone; pressure; receptive field; recombinant virus; relating to nervous system; response; spreading depression

 DESCRIPTION (provided by applicant): Occipital headache can be a prominent feature of both migraine and non-migraineous headaches. One third of all migraines begin with tenderness of neck and shoulder muscles that gradually develop into a low-grade occipital headache. Sensations of cramp, tension, stiffness, tenderness or pain in neck and shoulder muscles that radiate to the back of the head are also common in tension-type headache, cervicogenic headache and Chiari malformation. One of the many speculations on the cause of occipital headache states that compression, irritation or inflammation of the C2 sensory root can be a trigger - a view supported by C2 nerve stimulation that evokes occipital pain and by documented relief of such headaches by C2 blockade. Given the above, it is surprising how little is known about the innervation of the dura overlying the cerebellum and occipital cortex, and even more so, how little is known about the functional properties of peripheral neurons that innervate the posterior fossa or the central neurons that process nociceptive information from this area. The broad objective of this proposal is to define the neural substrate of occipital headaches. Our working hypothesis is that occipital headaches involve activation of (a) meningeal nociceptors in the C2 DRG that innervate the dura overlying the cerebellum and (b) central neurons that process this information. This working hypothesis will be tested in one anatomical and two physiological studies. In the anatomical study, we will use a recombinant adeno-associated virus containing a green fluorescent protein reporter gene to infect C2 DRG cells and map the course of their axons and their distribution in the intracranial dura. In the physiological studies we will identify peripheral neurons in C2 DRG and central neurons in C1-3 dorsal horn whose receptive fields are located in the posterior dura overlying the cerebellum and spinomedullary junction, and determine whether their responses can be sensitized by stimulation of their dural and muscle receptive fields. 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 C2/C3 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 triggers/causes of activation of nociceptors in the posterior dura (as compared to triggers of activation of nociceptors in the anterior dura) can lead to a deeper understanding of the neural basis of occipital headache and whether its origin differ from the origin of frontal/periorbital headache. RELEVANCE: A large number of migraine and non-migraine headache patients experience pain in the back of the head (occipital headache). This grant proposal will test the hypothesis that pain signals originating in the posterior dura are transmitted through meningeal nociceptors whose cell bodies are located in C2 DRG to upper cervical dorsal horn neurons that process sensory/nociceptive signals from the occipital dura, skin and muscles of the neck.

 描述（由申请人提供）：枕部头痛可能是偏头痛和非偏头痛的一个显着特征，三分之一的偏头痛始于颈部和肩部肌肉压痛，逐渐发展为低度的枕部痉挛感。颈肩部肌肉紧张、僵硬、压痛或疼痛放射至后脑勺，也常见于紧张型头痛、颈源性头痛和 Chiari 畸形。关于枕部头痛原因的众多推测之一是，C2 感觉根的压迫、刺激或炎症可能是触发因素——刺激 C2 神经引起枕部疼痛以及有记录的 C2 阻滞可缓解此类头痛的观点都支持这一观点。鉴于上述情况，令人惊讶的是，我们对覆盖小脑和枕叶皮层的硬脑膜的神经支配知之甚少，更重要的是，对支配小脑和枕叶皮层的外周神经元的功能特性知之甚少。该提案的主要目标是确定枕骨头痛的神经基础，即枕骨头痛涉及 (a) C2 DRG 中的脑膜伤害感受器的激活。支配小脑上方的硬脑膜和（b）处理该信息的中枢神经元将在一项解剖学和两项生理学研究中进行测试。在这项研究中，我们将使用含有绿色荧光蛋白报告基因的重组腺相关病毒感染 C2 DRG 细胞，并绘制其轴突的走向及其在颅内硬脑膜中的分布。在生理研究中，我们将识别 C2 DRG 中的周围神经元。和 C1-3 背角的中枢神经元，其感受野位于小脑和脊髓连接处上方的后硬脑膜，并确定它们的反应是否可以敏化在临床上，拟议的动物研究有可能为颅骨周围组织开始的枕骨头痛与颅内开始的枕骨头痛的不同提供新的线索，这些发现可能会扩大我们对 C2 的理解。 /C3 治疗常用于治疗偏头痛和非偏头痛；假设它是通过减少沿神经传导的伤害性信号来介导的枕神经包括减少源自后硬脑膜的伤害性信号，有可能识别新的触发因素/原因。 后硬脑膜中伤害感受器的激活（与前硬脑膜中伤害感受器激活的触发因素相比）可以使人们更深入地了解枕部头痛的神经基础以及其起源是否与额叶/眶周头痛的起源不同。 相关性：大量偏头痛和非偏头痛患者会出现后脑疼痛（枕骨头痛），该拨款提案将检验以下假设：源自后硬脑膜的疼痛信号是通过其细胞体为脑膜的伤害感受器传递的。位于 C2 DRG 至上颈背角神经元，处理来自枕骨硬脑膜、皮肤和颈部肌肉的感觉/伤害信号。