Project #3 In vivo microneurography recordings of sensory afferents

偏头痛是最常见的原发性头痛疾病之一，每四个美国家庭中就有一个受到影响。这个建筑群 神经功能障碍的部分原因是三叉神经躯体感觉的改变，表现为头/脸-头-面-头-面-头-头-面-面 三叉神经痛和/或三叉神经痛。偏头痛的有效治疗方法仍然有限，我们对 人类三叉神经系统在基线和偏头痛的情况下是稀疏的。响应RFA-NS-22-018，修复 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 成立宾夕法尼亚人类精确疼痛中心(Penn HPPC)，以阐明分子、细胞、表观遗传学和 人三叉神经节(TG)感觉神经元在基线和偏头痛状态下的生理特征。 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调查人员组成。这个 PI、两个MPI和两个协同IS目前正在合作研究人类背根的单胞体深度RNA序列 神经节(DRG)神经元项目，为这一应用奠定了坚实的基础。具体地说，宾夕法尼亚大学的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- 我，Nagi博士，是国际知名的人类感觉传入电生理学家，并得到Dr。 Li，数据核心的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- NILES、躯体感觉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 在体超声引导下对三叉神经和脊髓感觉神经传入进行显微神经学记录 这些偏头痛患者和对照组，使用一种新开发的刺激方案。我们的超声引导微型 神经成像技术大大提高了实验产量。新的刺激方案是根据- 人背根神经节神经元的单胞体深度RNA-SEQ数据，允许复杂的特征 偏头痛患者与对照组初级感觉传入的比较。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人类初级感觉传入的功能数据集。同舟共济 根据项目1和项目2的结果，我们提议的宾夕法尼亚大学HPPC将产生全面、多维的 人类TGS在基线和偏头痛条件下的分子和功能数据集。

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.