Nociceptive Afferent Topographical Innervation of the Heart and Stomach
心脏和胃的伤害性传入地形神经支配
基本信息
- 批准号:10263240
- 负责人:
- 金额:$ 45.97万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-19 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAbdomenAbdominal PainAfferent NeuronsAmericanAnatomyAnimalsAtlasesAxonCardiacCeliac ganglionCell NucleusChestChest PainComplexCoronary heart diseaseDataDevelopmentFemaleFutureGangliaGastrointestinal tract structureHeartHeart AtriumHeart failureIncidenceIndividualInjectionsLabelLeftLocationMammalsMapsMediatingMolecularMotorNerveNociceptionNodose GanglionOrganOrgan SpecificityPainPain MeasurementPain managementPeripheralPersonsPhysiologicalPhysiological ProcessesPresynaptic TerminalsPrevalenceProcessRattusResourcesSex DifferencesSideSpinalSpinal GangliaStomachStructureTRPV1 geneTaxonomyTechniquesTherapeutic InterventionTracerVisceralVisceral painWorkafferent nervechronic abdominal painchronic painheart innervationimprovedmalemicroscopic imagingnerve supplyneural circuitnon-opioid analgesicreceptive fieldreconstructionscaffoldsex
项目摘要
More than 50 million Americans suffer from chronic pain. Of those, 25 million live with daily chronic pain
and lack effective and safe non-opioid options for pain management. In particular, the new incidence of chest
pain is 15.5 per 1000 person-years, which is highly related to coronary heart disease and heart failure. In
addition, the prevalence of chronic abdominal pain is around 22.9 per 1,000 person-years. A large percentage
of abdominal pain is related to the gastrointestinal tract (GI). However, the anatomical and physiological
mechanisms of peripheral nociceptive processes have not been well studied. In this study, we aim to perform a
comprehensive anatomical mapping of pain-related neural circuitry in two visceral organs: heart (Aim 1) and
stomach (Aim 2). Nociception, from these organs in mammals, is mainly mediated by sensory neurons in the
spinal dorsal root ganglia (DRG) and to a lesser extent in the vagal nodose-jugular ganglion complex (for short:
nodose ganglion, seen below). Previously, Dr. Powley’s group and Dr. Cheng’s group have studied vagal
afferent and efferent as well as sympathetic efferent innervations of the heart and stomach, and their different
types of terminal structures (taxonomy) in whole mounts of atria and the stomach. To do so, we used a
combination of techniques, including tracer injections, anterograde tracing of axon distributions and terminal
structures, and microscopic imaging. However, the study of specific nociceptive nerve topographical
innervation in the heart and stomach is not well studied because such elegant, powerful, and challenging
techniques above have not yet been well applied in the spinal DRG. In this study, we will inject different tracers
into the DRG (left or right: C7-T5 for Heart; left or right: T6-T12 for Stomach) and into the vagal nodose
ganglia (left or right: for both Heart and Stomach) for anterograde labeling of sensory nerve innervation. In
addition, we will also use immunohistochemical (IHC) labeling of CGRP, SP, and TRPV1 (the three nociceptive
nerve markers) in tracer-injected animals that will specifically identify the nociceptive afferent innervation of
these organs from distinct origins (spinal, vagal, or left/right side). The topographical innervation map will be
annotated and presented in the 3D reconstructed heart and stomach, and then their 3D scaffolds of these
organs (Aim 3). We will also assess for organ specificity (nociceptive innervation that distinguishes the heart
and stomach from each other), left or right sidedness of ganglia, and sex differences. Comprehensive and
topographical mapping of nociceptive afferent innervation of these organs will substantially improve the
understanding of physiological processes in relation to nociception. This mapping data will also aid to develop
new selective interventional therapies/stimulations for visceral pain of these organs.
超过5000万美国人患有慢性疼痛。其中2500万人每天都有慢性疼痛
缺乏有效和安全的非阿片类药物治疗疼痛的选择。特别是,胸部新发病率
疼痛为15.5/1000人-年,与冠心病和心力衰竭高度相关。在
此外,慢性腹痛的患病率约为每1 000人年22.9例。很大比例
腹痛与胃肠道(GI)有关。然而,解剖学和生理学
外周伤害感受过程的机制尚未得到很好的研究。在这项研究中,我们的目标是执行一个
在两个内脏器官中与疼痛相关的神经回路的全面解剖映射:心脏(目标1)和
胃(目标2)。来自哺乳动物这些器官的伤害感受主要由皮层中的感觉神经元介导。
脊髓背根神经节(DRG)和迷走神经结-颈静脉神经节复合体(简称:
结状神经节,见下文)。此前,Powley博士的小组和Cheng博士的小组研究了迷走神经
心脏和胃的传入和传出以及交感传出神经支配,以及它们的不同
心房和胃的整个安装中的终端结构类型(分类学)。为此,我们使用了
结合技术,包括示踪剂注射,轴突分布的顺行追踪和终端
结构和显微成像。然而,特定伤害性神经地形图的研究
心脏和胃的神经支配没有得到很好的研究,因为这种优雅,强大,具有挑战性的
上述技术尚未很好地应用于脊柱DRG。在这项研究中,我们将注入不同的示踪剂,
进入DRG(左或右:心脏的C7-T5;左或右:胃的T6-T12)并进入迷走神经结
神经节(左侧或右侧:心脏和胃),用于感觉神经支配的顺行标记。在
此外,我们还将使用CGRP,SP和TRPV 1(三种伤害性感受因子)的免疫组织化学(IHC)标记,
神经标记物),这将特异性地识别
这些器官来自不同的起源(脊髓、迷走神经或左/右侧)。地形神经分布图将
注释并在3D重建的心脏和胃中呈现,然后它们的3D支架
器官(目标3)。我们还将评估器官特异性(区分心脏的伤害性神经支配
和胃),神经节的左侧或右侧,以及性别差异。全面和
这些器官的伤害性传入神经支配的地形图将显著改善
了解与伤害感受有关的生理过程。这些地图数据也将有助于开发
新的选择性介入治疗/刺激这些器官的内脏疼痛。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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ZIXI Jack CHENG其他文献
ZIXI Jack CHENG的其他文献
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{{ truncateString('ZIXI Jack CHENG', 18)}}的其他基金
Nociceptive Afferent Topographical Innervation of the Heart and Stomach
心脏和胃的伤害性传入地形神经支配
- 批准号:
10266322 - 财政年份:2019
- 资助金额:
$ 45.97万 - 项目类别:
Nociceptive Afferent Topographical Innervation of the Heart and Stomach
心脏和胃的伤害性传入地形神经支配
- 批准号:
10021470 - 财政年份:2019
- 资助金额:
$ 45.97万 - 项目类别:
Chronic Intermittent Hypoxia: Sympathetic and Intrinsic Cardiac GanglionicInnervation
慢性间歇性缺氧:交感神经和内在心脏神经节神经支配
- 批准号:
9516205 - 财政年份:2018
- 资助金额:
$ 45.97万 - 项目类别:
Cardiac Neuropathy in Type 1 Diabetic and Aging
1 型糖尿病患者的心脏神经病变与衰老
- 批准号:
7123381 - 财政年份:2004
- 资助金额:
$ 45.97万 - 项目类别:
Cardiac Neuropathy in Type 1 Diabetic and Aging
1 型糖尿病患者的心脏神经病变与衰老
- 批准号:
6950009 - 财政年份:2004
- 资助金额:
$ 45.97万 - 项目类别:
Cardiac Neuropathy in Type 1 Diabetic and Aging
1 型糖尿病患者的心脏神经病变与衰老
- 批准号:
7279129 - 财政年份:2004
- 资助金额:
$ 45.97万 - 项目类别:
LASER SCANNING CONFOCAL MICROSCOPE: NEUROSCIENCE
激光扫描共焦显微镜:神经科学
- 批准号:
6973661 - 财政年份:2004
- 资助金额:
$ 45.97万 - 项目类别:
Aging, Hypoxia, and Sympathetic Cardiac Projections
衰老、缺氧和交感心脏投射
- 批准号:
6727120 - 财政年份:2004
- 资助金额:
$ 45.97万 - 项目类别:
Cardiac Neuropathy in Type 1 Diabetic and Aging Mice
1 型糖尿病和衰老小鼠的心脏神经病变
- 批准号:
6879351 - 财政年份:2004
- 资助金额:
$ 45.97万 - 项目类别:
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