Neural Basis of Occipital Headache

 描述(申请人提供)：枕部头痛可以是偏头痛和非偏头痛的显著特征。三分之一的偏头痛始于颈部和肩部肌肉的压痛，逐渐发展为轻度枕部头痛。在紧张型头痛、颈源性头痛和Chiari畸形中，颈部和肩部肌肉的抽筋、紧张、僵硬、压痛或疼痛的感觉也很常见，这些肌肉辐射到脑后。关于枕部头痛原因的众多推测之一指出，C2感觉神经根的压迫、刺激或炎症可能是触发因素--C2神经刺激引起枕部疼痛，并通过C2阻断缓解此类头痛，这一观点得到了支持。鉴于上述情况，令人惊讶的是，人们对覆盖在小脑和枕叶皮质上的硬脑膜的神经支配知之甚少，更令人惊讶的是，对支配后颅窝的外周神经元或处理该区域伤害性信息的中枢神经元的功能特性知之甚少。这项建议的广泛目标是确定枕部头痛的神经基础。我们的工作假设是，枕部头痛涉及(A)C2 DRG中支配小脑上方硬脑膜的脑膜伤害性感受器的激活，以及(B)处理这一信息的中枢神经元的激活。这一工作假说将在一项解剖学研究和两项生理学研究中得到验证。在解剖学研究中，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，并绘制其轴突的轨迹及其在硬脑膜中的分布。在生理学研究中，我们将确定C2背根节的外周神经元和C1-3背角的中枢神经元，其感受野位于小脑和脊髓延髓交界处的后硬脑膜，并确定刺激它们的硬脑膜和肌肉感受野是否能敏化它们的反应。在临床上，拟议的动物研究有可能为始于颅周组织的枕部头痛与开始于颅内的枕部头痛有何不同之处提供新的线索。在治疗上，这些发现可能会扩大我们对C2/C3手法常用于偏头痛和非偏头痛治疗的理解；从假设它是通过减少沿枕神经传播的伤害性信号介导，到包括减少起源于硬脑膜后的伤害性信号。科学上，确定新的触发因素/原因的可能性 后硬脑膜伤害性感受器的激活(与前硬脑膜伤害性感受器的激活相比)可以使我们更深入地了解枕部头痛的神经基础，以及它的起源是否有别于额部/眶周头痛的起源。 相关性：大量偏头痛和非偏头痛患者会经历后脑勺疼痛(枕部头痛)。这项拨款建议将检验以下假设：源自硬脑膜后段的疼痛信号通过位于C2背根节的脑膜伤害性感受器传递到上颈背角神经元，后者处理来自枕部硬脑膜、皮肤和颈部肌肉的感觉/伤害性信号。

 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.