Trigeminal Pain Pathways

三叉神经疼痛通路

基本信息

批准号：
7892446
负责人：
SUE A AICHER
金额：
$ 38.12万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-02-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7892446
关键词：
Adult Afferent Neurons American Animals Area Brain Chemicals Complement component C1s Confocal Microscopy Contact Lenses Cornea Corneal Injury Craniofacial Pain Data Elderly Electron Microscopy Elements Frequencies Future Glutamates Goals Heating Interneurons Knowledge Laser In Situ Keratomileusis Mechanics Mediating Neural Pathways Neuronal Plasticity Neurons Neurotransmitter Receptor Neurotransmitters Nociception Nociceptors Ophthalmologic Surgical Procedures Orofacial Pain Output Pain Pathway interactions Pattern Perception Phenotype Physiological Population Process Public Health Reflex action Regulation Relative (related person)Sensory Source Stimulus Structure Synapses TRPV1 gene Target Populations Testing Thalamic structure Tissues Travel Trigeminal Neuralgia Trigeminal System Uveitis Work base cellular targeting chronic pain design dorsal horn effective therapy eye dryness follow-up molecular marker postsynaptic public health relevance receptor regional difference relating to nervous system response therapeutic target

项目摘要

DESCRIPTION (provided by applicant): Effective treatment of craniofacial pain requires knowledge of the relationships between neural structures, neurotransmitters and receptors that may be therapeutic targets. The physiological basis for these relationships is grounded in the anatomical arrangements between primary afferents, descending projections, interneurons, and efferent projection neurons in the trigeminal dorsal horn. The long-term goal of this work is to understand the anatomical relationship between neuronal elements that mediate or modulate nociception in the trigeminal dorsal horn. The proposed studies use corneal afferents as a nociceptive marker and will examine the relationships between these afferents and other neurons, including interneurons, projection neurons, and descending inputs, in the trigeminal dorsal horn. Studies in Aim 1 will determine if corneal afferents target inhibitory interneurons, trigeminothalamic or trigeminopontine projection neurons; thus defining the basic connectivity of these afferents. Corneal afferents project to two distinct regions of trigeminal dorsal horn, and these regions are thought to mediate functionally distinct components of corneal nociception. Preliminary data demonstrate that the neurotransmitter and transporter content of corneal afferent projections to these two regions are distinct. In Aim 2, differences in the expression of neuronal markers will be examined in corneal afferents, including various putative sensory transduction molecules. Additional studies will determine if select populations of corneal afferents target specific populations of target neurons defined in Aim 1. In Aim 3, the targets of descending medullary projections will be examined to determine if these neurons converge on similar neurons with corneal afferents. Together these studies will provide a more specific understanding of the anatomical relationships between corneal afferents and descending afferent projections, inhibitory interneurons and efferent projection neurons within the trigeminal dorsal horn. These results will provide information about the anatomical substrates for ocular pain and potential mechanisms for both neuronal plasticity and therapeutic targets in the trigeminal dorsal horn. PUBLIC HEALTH RELEVANCE Orofacial pain represents a significant public health concern, afflicting more than 10% of adults, and 50% of elderly adults. Pain arising from corneal injury is on the rise due to the increased number of Americans undergoing refractive eye surgery, including PRK and LASIK (Belmonte, 2004, 2007). Other sources of ocular pain include dry eye, uveitis, and contact lens use. The studies in this proposal are designed to understand the neural pathways involved in transmitting pain from the cornea to the brain.

描述（由申请人提供）：有效治疗颅面疼痛需要了解可能是治疗靶标的神经结构，神经递质和受体之间的关系。这些关系的生理基础是基于三叉角角的主要传入，降量投影，中间神经元和传出的投射神经元之间的解剖学布置。这项工作的长期目标是了解介导或调节三叉角角伤害感受的神经元元素之间的解剖学关系。拟议的研究使用角膜传入作为伤害性标记，并将检查这些传入者与其他神经元之间的关系，包括中间神经元，投影神经元和降降性输入，在三叉角背角中。 AIM 1中的研究将确定角膜传入是否靶向抑制性中间神经元，三角甲丘脑或三角骨trigeminopontine投射神经元；从而定义了这些传入的基本连通性。角膜传入向三叉角角的两个不同区域进行项目，并且这些区域被认为可以介导角膜伤害感受的功能不同的成分。初步数据表明，对这两个区域的角膜传入投影的神经递质和转运蛋白含量是不同的。在AIM 2中，将在角膜传入（包括各种推定的感觉转导分子）中检查神经元标记的表达差异。进一步的研究将确定是否针对AIM 1中定义的目标神经元的特定目标群体的选择群体。在AIM 3中，将检查降髓突发性的靶标，以确定这些神经元是否会在具有角膜传入的类似神经元上汇聚。这些研究将共同对角膜传入和传入的降低预测，抑制性中间神经元和传出投射神经元之间的解剖学关系提供更具体的理解。这些结果将提供有关三叉角角中神经元可塑性和治疗靶标的眼部疼痛和潜在机制的解剖底物的信息。公共卫生相关性的类种族疼痛代表了公共卫生的重大关注，折磨了超过10％的成年人和50％的老年人。由于角膜损伤引起的疼痛正在增加，这是由于包括PRK和LASIK在内的美国人接受折射力手术的数量增加（Belmonte，2004，2007）。眼部疼痛的其他来源包括干眼症，葡萄膜炎和隐形眼镜使用。该提案中的研究旨在了解将疼痛从角膜传播到大脑的神经途径。