Linking trigeminal and visual sensitivity in migraine

将三叉神经和视觉敏感性与偏头痛联系起来

• 批准号: 10578898
• 负责人: Geoffrey Karl Aguirre
• 金额: $ 44.69万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-19 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10578898
• 关键词: Air; Anatomy; Animals; Auras; Biological Markers; Biological Models; Biology; Blinking; Brain Concussion; Brain Stem; Cells; Chemosensitization; Cornea; Data; Diffuse; Dimensions; Disease; Elements; Esthesia; Face; Fibromyalgia; Functional Magnetic Resonance Imaging; Headache; Human; Hypersensitivity; Individual Differences; Judgment; Light; Lighting; Link; Measurement; Measures; Meninges; Migraine; Modeling; Neurologic; Nociception; Ophthalmology; Pain; Persons; Phase; Photic Stimulation; Photophobia; Photoreceptors; Photosensitivity; Physiologic pulse; Production; Property; Psychophysics; Reflex action; Reporting; Reproducibility; Retina; Retinal Ganglion Cells; Rodent; Role; Sensory; Signal Transduction; Site; Stimulus; Symptoms; Tactile; Testing; Thalamic structure; Touch sensation; Trigeminal System; Trigeminal nerve structure; Variant; Visual; Visual system structure; Work; allodynia; blink reflexes; experience; eye dryness; indexing; melanopsin; pressure; programs; relating to nervous system; response; somatosensory

Project Summary Hypersensitivity is a canonical feature of migraine, with pain from light (photophobia) and touch (facial allodynia) present during the ictal headache phase, and sometimes the inter-ictal period as well. Headache and facial allodynia appear to reflect potentiation of trigeminal signals in migraine. This same mechanism may account for photophobia as well. A subset of retinal ganglion cells express the photopigment melanopsin, rendering them intrinsically photosensitive (the “ipRGCs”). Rodent studies show that these cells project to thalamic and brainstem sites that also receive somatosensory input from the trigeminal nerve, providing a point of neural interaction of somatic and visual signals. Can this promising biological model—derived in animal studies—account for the properties of sensory symptoms in human migraine? To explore this question, we require a quantitative hypothesis testing framework, and a reproducible, objective measure of trigeminal sensitivity to supra-threshold stimuli. We propose to create this experimental platform and test key elements of the trigeminal hypersensitivity model. We have modified a commercial “blink reflexometer” to measure parameters of the corneal blink reflex to graded air-puff stimulation. We will test (Aim 1) if people with migraine and inter-ictal photophobia, as compared to headache-free controls, have a systematic, group difference in the slope of this reflexive sensitivity function or in a report of discomfort. Further, we will determine (Aim 2) if graded variation in a simultaneous light stimulus interacts with air-puff intensity in the production of these explicit and reflexive responses, thereby testing for anatomical convergence of visual and trigeminal somatic signals.

项目摘要 过敏是偏头痛的典型特征，伴随着来自光（恐光症）和触摸（面部）的疼痛。 异常性疼痛）出现在发作性头痛阶段，有时也出现在发作间期。头痛 和面部异常性疼痛似乎反映了偏头痛中三叉神经信号的增强。同样的机制可以 这也是恐惧症的原因视网膜神经节细胞的一个亚群表达黑视素， 使它们具有本征光敏性（“ipRGC”）。啮齿动物的研究表明，这些细胞投射到 丘脑和脑干部位也接受来自三叉神经的躯体感觉输入， 身体和视觉信号的神经互动。这种有前途的生物模型能否在动物中获得 研究-解释人类偏头痛感觉症状的特性？为了探讨这个问题，我们 需要一个定量的假设检验框架，和一个可重复的，客观的测量三叉神经 对阈上刺激的敏感性。我们建议创建这个实验平台，并测试 三叉神经超敏反应模型。我们艾德了一个商业“眨眼反射计”， 角膜眨眼的参数对分级的吹气刺激的反应。我们将测试（目标1）是否有偏头痛的人 与无头痛的对照组相比，发作间期头痛恐怖症患者的头痛发生率存在系统性组间差异。 该反应灵敏度函数的斜率或不适的报告。此外，我们将确定（目标2），如果 在同时光刺激的分级变化与空气抽吸强度相互作用， 外显和反射反应，从而测试视觉和三叉神经躯体的解剖学会聚 信号.