Mechanisms of Pain and Photophobia in Migraine and Dry Eye

偏头痛和干眼症的疼痛和畏光机制

基本信息

批准号：
10707192
负责人：
SUE A AICHER
金额：
$ 100.77万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-30 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10707192
关键词：
Afferent Neurons Anatomy Automobile Driving Behavior Behavioral Cd68 Cells Confocal Microscopy Cornea Development Dry Eye Syndromes Dura Mater Electron Microscopy Electrophysiology (science)Eye Eye Development FDA approved Feedback Female Gap Junctions Homeostasis Hypersensitivity Immune Immune system Infiltration Investigation Iris Light Measures Mediating Methods Migraine Modeling Molecular Nerve Neural Pathways Neuroanatomy Neuroglia Neurons Nociceptors Operative Surgical Procedures Pain Pathway interactions Patients Persistent pain Pharmacological Treatment Phenotype Photophobia Physiological Population Proteins Proteomics Pupil light reflex Reflex action Regulation Research Retina Rodent Model Sensory Stimulus Structure of trigeminal ganglion Surgical Models System TRP channel Testing Tissues Touch sensation Trigeminal System Trigeminal nerve structure Up-Regulation afferent nerve antagonist corneal epithelium density experience experimental study eye dryness immune cell infiltrate immunocytochemistry melanopsin nerve injury neurochemistry non-opioid analgesic novel ocular pain pain model pain sensation pharmacologic protein expression response targeted agent therapeutic development therapeutic target tissue injury

项目摘要

Project Summary Ocular pain and photophobia are common and debilitating conditions associated with migraine and dry eye disease (DED). Persistent pain, dry eye, and/or photophobia are also experienced by nearly 40% of patients who have received refractive surgery. A common neuroanatomical substrate in migraine, DED, and refractive surgery is the trigeminal nerve, specifically the ophthalmic branch, which is involved in reflex homeostatic regulation of the cornea and dura. It is well known that damage to these reflex circuits leads to overt sensations of pain, yet the underlying mechanisms are poorly understood and effective non-opioid treatments are lacking. We hypothesize that the trigeminal neurons projecting to the cornea and dura are modulated by feedback from light-sensing cells in the eye, as well as by interaction with infiltrating immune cells leading to dysregulation of the reflex pathways and amplification of sensory responses – causing hypersensitivities to touch and light (photophobia). We will test this hypothesis in rodent models of migraine, DED, and refractive surgery by identifying molecular mechanisms and neural pathways common to the three pain models, using neuroanatomical, physiological, and behavioral approaches. Experiments will include investigation of potential therapeutic targets, including CGRP, TRPM3, and melanopsin, all of which have been previously implicated in photophobia. These studies will elucidate key cellular and molecular changes underlying the development of ocular pain and photophobia in migraine, DED, and refractive surgery, and will guide therapeutic development.

项目概要眼痛和畏光是与偏头痛和干眼症相关的常见且令人衰弱的病症近 40% 的患者还患有持续性疼痛、干眼症和/或畏光症。接受过屈光手术的人是偏头痛、DED 和屈光的常见神经解剖学基础。手术是三叉神经，特别是眼支，它参与反射稳态众所周知，这些反射回路的损伤会导致明显的角膜和硬脑膜的调节。疼痛感，但其潜在机制知之甚少，并且有效的非阿片类药物治疗我们认为投射到角膜和硬脑膜的三叉神经元受到调节。来自眼睛光敏细胞的反馈，以及与浸润免疫细胞的相互作用，导致反射通路失调和感觉反应放大——导致过敏我们将在偏头痛、DED 和屈光的啮齿动物模型中检验这一假设。通过识别三种疼痛模型共有的分子机制和神经通路，使用实验将包括神经解剖学、生理学和行为方法的研究。治疗靶点，包括 CGRP、TRPM3 和黑视蛋白，所有这些先前都与这些研究将阐明畏光发展背后的关键细胞和分子变化。偏头痛、DED 和屈光手术中的眼痛和畏光，并将指导治疗的发展。