Project #3 In vivo microneurography recordings of sensory afferents

项目

• 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
• 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

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，影响四分之一的美国家庭。这个复杂 神经障碍部分由三叉神经躯体感觉的改变介导，三叉神经躯体感觉的改变表现为头/发- 坐骨神经痛和/或三叉神经异常性疼痛。偏头痛的有效治疗方法仍然有限，我们对偏头痛的认识 人三叉神经系统在基线和偏头痛条件下是稀疏的。响应RFA-NS-22-018，HEAL 计划：人类疼痛相关基因和细胞的发现和功能评价，我们建议 成立宾州人类精确疼痛中心（Penn HPPC），以阐明分子，细胞，表观遗传， 在基线和偏头痛条件下的人三叉神经节（TG）感觉神经元的生理概况。 Penn HPPC将由具有多学科专业知识的Penn和国际研究人员组成。的 PI，两个MPI和两个co-I目前正在合作进行人类背根的单细胞体深层RNA测序 神经节（DRG）神经元项目，这为该应用奠定了坚实的基础。具体来说，Penn HPPC 将包含三个核心并执行三个项目。项目3将由主要研究者Olausson博士和共同研究者领导。 我，博士Nagi，谁是国际知名的人类感觉传入电生理学家，并支持博士。 李，PI的数据核心。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- naires，躯体感觉测试和眨眼反射，以评估其感觉和运动功能。在目标2中，我们 进行三叉神经和脊髓感觉传入的体内超声引导显微神经造影术记录， 这些偏头痛患者和对照组，使用新开发的刺激协议。我们的超声波引导微- 神经造影技术大大提高了实验产率。新的刺激协议是根据雅阁设计的- 与人类DRG神经元单胞体深度RNA-seq数据相结合，允许对 偏头痛患者和对照组之间的初级感觉传入和比较。简而言之，预期的重新- 来自项目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的人类初级感觉传入的功能数据集。一起 根据项目1和项目2的结果，我们提出的宾夕法尼亚大学HPPC将产生全面的、多维度的 在基线和偏头痛条件下的人TG的分子和功能数据集。