Human Nociceptor and Spinal Cord Molecular Signature Center

人类伤害感受器和脊髓分子特征中心

• 批准号: 10707528
• 负责人: Michele Curatolo
• 金额: $ 227.42万
• 依托单位: UNIVERSITY OF TEXAS DALLAS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-19 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10707528
• 关键词: Adult; Afferent Neurons; Animal Model; Animals; Architecture; Biological Assay; Brain; Cancer Center; Cell Nucleus; Cells; Chest; Chronic disabling pain; Chronic low back pain; Chronic neck pain; Collaborations; Communication; Complex; Data; Disease; Ensure; Foundations; Generations; Genome; Genomics; Goals; Human; Immunohistochemistry; Individual; Information Resources; Longevity; Low Back Pain; Maps; Methods; Microfluidics; Modeling; Molecular; Molecular Analysis; Molecular Profiling; Mus; Nature; Nerve; Neurons; Nociception; Nociceptors; Operative Surgical Procedures; Organ Donor; Pain; Pain management; Pathway interactions; Patients; Peripheral; Peripheral Nerves; Pharmacology; Physiological; Population Heterogeneity; Posterior Horn Cells; Price; Process; Productivity; Protocols documentation; Publications; Publishing; Quality Control; RNA; Research Personnel; Research Project Grants; Resolution; Resources; Sampling; Sex Differences; Signal Transduction; Spinal; Spinal Cord; Spinal Ganglia; Split-Pool Ligation Transcriptome sequencing; Synapses; Techniques; Technology; Therapeutic; Tissue Procurements; Tissues; Translations; Universities; Vertebral column; Washington; Work; cell type; chronic pain; chronic painful condition; conflict resolution; connectome; data resource; dorsal horn; empowerment; human tissue; insight; molecular phenotype; nonhuman primate; pain patient; pain perception; painful neuropathy; ribosome profiling; sex; success; tissue processing; transcriptome; transcriptome sequencing; transcriptomics

Our collaborative groups, led by Drs. Price at UT Dallas (UTD), Dougherty at MD Anderson Cancer Center (MDACC) and Curatolo at University of Washington (UW), have been on the forefront of using human dorsal root ganglion (DRG) and other tissues to understand mechanisms that cause chronic pain in patients. Our work is on the leading edge of transcriptomic studies that have revealed unique features of the human DRG at the single neuron level. The goal of this project is to create the scientific foundation that will empower pain researchers around the world to approach the problem of treating pain in a new way, deeply rooted in a fundamental understanding of the first neurons and first synapses in the pain pathway. Our Center will focus on two prioritized aims. The first is identifying molecular phenotypes, using single cell and spatial transcriptomic technologies, of human sensory neurons from the DRG in organ donor recovered tissues and in patients suffering from chronic pain who are having surgeries where DRGs or peripheral nerves are removed. We will use this information to understand how nociceptors are activated in chronic pain disorders, with a focus on neuropathic pain, chronic neck pain and low back pain. These chronic pain disorders are the most disabling and the latter two are poorly modeled in animals. The second is to use spinal cord recovered from organ donors for single cell and spatial profiling with the goal of understanding the connectome of the human pain pathway at the first synapse. We will provide an integrated view of how nociceptors likely communicate with spinal cord neurons with the goal of understanding the pharmacology of projection neurons that send nociceptive signals to the brain to create pain perception. Our established collaboration and demonstrated track record of productivity ensures the success of this complex project. We envision creating actionable knowledge and data resources that can transform our understanding of human pain conditions leading to the generation of the treatments pain patients need.

我们的合作小组由德克萨斯大学达拉斯分校的普莱斯博士、MD安德森癌症中心的多尔蒂博士领导 (MDACC)和华盛顿大学(UW)的库拉托罗(Curatolo)，一直走在利用人类背部 根神经节(DRG)和其他组织，以了解导致患者慢性疼痛的机制。我们的工作 处于转录学研究的前沿，这些研究揭示了人类DRG在 单神经元水平。这个项目的目标是建立科学基础，使疼痛成为可能 世界各地的研究人员以一种新的方式处理疼痛问题，深深植根于 对疼痛通路中的第一个神经元和第一个突触有基本的了解。我们的中心将专注于 两个优先考虑的目标。第一个是利用单细胞和空间转录鉴定分子表型。 人类背根节感觉神经元在器官捐赠者康复组织和患者中的技术 由于慢性疼痛，他们正在接受手术，移除背根节或周围神经。我们将使用这个 了解慢性疼痛障碍中伤害性感受器是如何被激活的信息，重点是神经性疾病 疼痛、慢性颈痛和腰痛。这些慢性疼痛障碍的致残率最高，而后者 其中两个是在动物身上模拟得很差的。第二种是将从器官捐赠者那里回收的脊髓用于单个细胞 和空间侧写，目标是首先了解人类疼痛路径的连接体 Synapse。我们将提供伤害性感受器如何与脊髓神经元沟通的综合观点。 目的是了解向大脑发送伤害性信号的投射神经元的药理学 来创造疼痛感知。我们已建立的协作和良好的工作效率记录确保 这个复杂项目的成功。我们设想创建可操作的知识和数据资源，以 改变我们对人类疼痛状况的理解，导致治疗疼痛患者的产生 需要。