Project #3 In vivo microneurography recordings of sensory afferents

项目

基本信息

批准号：
10806549
负责人：
Håkan Olausson
金额：
$ 85.02万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-20 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10806549
关键词：
Affect Afferent Neurons Auditory Behavioral Biological Markers Biology Brain Stem Cell Nucleus Cells Classification Clinical Cluster Analysis Collaborations Complex Coupled Data Data Analyses Data Set Databases Detection Diagnosis Dimensions Discrimination Electrophysiology (science)Epigenetic Process Evaluation Facial Pain Foundations Functional disorder Gene Expression Profiling Genes Genetic Genetic Databases Goals Head Headache Headache Disorders Health Helping to End Addiction Long-term Household Human Human Characteristics Hypersensitivity International Knowledge Measures Mechanics Mediating Methods Migraine Molecular Motor Nausea Neuroglia Neurons Nociception Nociceptors Pain Pain Clinics Patients Perception Physiological Process Property Protocols documentation Psychophysics Questionnaires RNA Reflex action Research Personnel Role Sensory Sensory Ganglia Skin Spinal Spinal Ganglia Spinal nerve structure Stimulus Structure Structure of trigeminal ganglion System Techniques Testing Time Trigeminal System Universities Vertebral column Visual Vomiting Withdrawal allodynia blink reflexes chronic pain chronic painful condition design effective therapy epigenome human RNA sequencing human subject improved in vivo mechanical stimulus migraine treatment multidisciplinary multiple omics nervous system disorder neuronal cell body neurotransmission new therapeutic target novel novel strategies peripheral pain pharmacologic recruit response single-cell RNA sequencing somatosensory transcriptome sequencing transcriptomics translational study ultrasound

项目摘要

Migraine, one of the most common primary headache disorders, affects 1 in 4 US households. This complex neurologic disorder is mediated in part by alterations in trigeminal somatosensation, which manifests as head/fa- cial pain and/or trigeminal allodynia. Effective treatments for migraine are still limited, and our knowledge about human trigeminal system at baseline and migraine conditions are sparse. In response to RFA-NS-22-018, HEAL Initiative: Discovery and Functional Evaluation of Human Pain-associated Genes & Cells, we propose to form the Penn Human Precision Pain Center (Penn HPPC) to elucidate molecular, cellular, epigenetic, and physiological profiles of human trigeminal ganglion (TG) sensory neurons at baseline and migraine conditions. The Penn HPPC will be composed of Penn and international investigators with multidisciplinary expertise. The PI, two MPIs, and two co-Is are currently collaborating on a single-soma deep RNA-seq of human dorsal root ganglion (DRG) neuron project, which form a strong foundation for this application. Specifically, the Penn HPPC will contain three cores and perform three projects. Project 3 will be led by the PI, Dr. Olausson, and the Co- I, Dr. Nagi, who are internationally renowned human sensory afferent electrophysiologists, and supported by Dr. Li, PI of the data core. In aim 1, we will recruit migraine patients and control subjects to conduct pain question- naires, somatosensory tests, and blink reflex to evaluate their sensory and motor functions. In aim 2, we will perform In vivo ultrasound-guided microneurography recordings of trigeminal and spinal sensory afferents with these migraine patients and controls, using a newly developed stimulus protocol. Our ultrasound guided micro- neurography technique greatly improves the experimental yield. The new stimulus protocol is designed accord- ing to the human DRG neuron single-soma deep RNA-seq data, allowing for sophisticated characterizations of primary sensory afferents and comparison between migraine patients and controls. In short, the anticipated re- sults from project 3, the electrophysiological and sensory results of migraineurs and controls, will generate novel functional datasets regarding human primary sensory afferents at baseline and migraine conditions. Together with results from projects 1 and 2, our proposed Penn HPPC will generate comprehensive, multi-dimensional molecular and functional datasets of human TGs at baseline and migraine conditions.

偏头痛是最常见的原发性头痛疾病之一，影响着四分之一的美国家庭。这个综合体神经系统疾病部分是由三叉神经躯体感觉的改变介导的，表现为头/fa- 关节疼痛和/或三叉神经异常性疼痛。偏头痛的有效治疗方法仍然有限，而且我们对偏头痛的了解人类三叉神经系统的基线和偏头痛状况很少。回应 RFA-NS-22-018，治愈倡议：人类疼痛相关基因和细胞的发现和功能评估，我们建议成立宾夕法尼亚州人类精准疼痛中心 (Penn HPPC)，以阐明分子、细胞、表观遗传和人类三叉神经节 (TG) 感觉神经元在基线和偏头痛条件下的生理特征。宾夕法尼亚大学 HPPC 将由宾夕法尼亚大学和具有多学科专业知识的国际研究人员组成。这 PI、两个 MPI 和两个 co-Is 目前正在合作开展人类背根的单体细胞深层 RNA 测序神经节（DRG）神经元项目，为该应用奠定了坚实的基础。具体来说，宾夕法尼亚州 HPPC 将包含三个核心并执行三个项目。项目 3 将由 PI、Olausson 博士和 Co- 领导我，Nagi 博士，国际知名的人类感觉传入电生理学家，并得到 Nagi 博士的支持。李，数据核心PI。在目标1中，我们将招募偏头痛患者和对照受试者进行疼痛问题- 奈尔、体感测试和眨眼反射来评估他们的感觉和运动功能。在目标 2 中，我们将对三叉神经和脊髓感觉传入进行体内超声引导显微神经造影记录这些偏头痛患者和对照组使用新开发的刺激方案。我们的超声波引导微神经造影技术大大提高了实验产量。新的刺激方案的设计符合获取人类 DRG 神经元单体深度 RNA-seq 数据，从而实现复杂的表征主要感觉传入以及偏头痛患者和对照组之间的比较。简而言之，预期的重新项目 3 的结果，偏头痛患者和对照组的电生理和感觉结果，将产生新的关于基线和偏头痛条件下人类初级感觉传入的功能数据集。一起根据项目 1 和 2 的结果，我们提出的 Penn HPPC 将产生全面的、多维的基线和偏头痛条件下人类 TG 的分子和功能数据集。