Project 2: The cell types and states of painful neuromas

项目 2：疼痛性神经瘤的细胞类型和状态

基本信息

批准号：
10594337
负责人：
CLIFFORD J WOOLF
金额：
$ 35.23万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
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/10594337
关键词：
Anatomy Architecture Automobile Driving Axon Binding Biochemical Pathway Blood Vessels Cells Clinical Data Collection Communities Data Data Collection Data Set Data Storage and Retrieval Development Development Plans Disease Excision Fibroblasts Functional disorder Genetic Transcription Goals Histologic Human Immune Immunofluorescence Immunologic Injury Knowledge Lead Ligands Link Local Anesthetics Mechanical Stimulation Mechanics Molecular Analysis Morphology Muscle Nerve Nerve Tissue Neuroglia Neuroma Neuronal Injury Neurons Pain Pain Clinics Pain management Pathologic Pathway interactions Patients Periodicity Peripheral Peripheral Nerves Phenotype Procedures Process Proteomics Research Sampling Schwann Cells Signal Pathway Signaling Molecule Site Source Stains Standardization Stretching System Time Transcript Trigeminal nerve structure axon injury biobank cell type chemotherapy clinical phenotype comorbidity diabetic differential expression genomic data genotyped patients insight limb amputation nerve injury nerve supply novel novel therapeutic intervention novel therapeutics pain reduction pain sensitivity painful neuropathy preclinical study protein expression receptor regenerative sciatic nerve single-cell RNA sequencing spatial relationship tool transcriptomics tumor growth

项目摘要

PROJECT SUMMARY (Project 2) We propose a plan for the development of a biobank of human neuroma and intact nerve tissues, accompanied by a comprehensive set of transcriptomic, proteomic, and histological analyses, to generate correlations and testable hypotheses on the mechanistic basis for the pain in painful neuromas and the active biochemical and signaling pathways that may contribute to this phenotype that will be an important tool for the pain community to identify the exact composition and spatial architecture of painful neuromas and the identification of those features that uniquely are present only in the presence of pain. Given that painful neuromas are a major source of peripheral neuropathic pain, and that recent data increasingly points to immune and glial cells as drivers of the pain by virtue of the signaling molecules that they produce to act on injured neurons, the data generated may realistically provide important and novel insight into the pathophysiology of neuropathic pain in patients which in turn could lead to the development of new therapeutic strategies. It is conceivable that the data may reveal that the drivers of pain may change with time and may be linked to the genotype of patients or coexisting diseases, features which preclinical studies will not reveal.

项目摘要（项目2）我们提出了一个计划，以发展人类神经瘤和完整神经组织的生物库，伴随着一组全面的转录组，蛋白质组学和组织学分析，以生成在疼痛神经瘤和活性的疼痛的机理基础上的相关性和可检验的假设可能有助于这种表型的生化和信号通路，这将成为重要的工具疼痛社区确定疼痛神经瘤和的确切组成和空间结构仅在疼痛的情况下识别那些独特的特征。鉴于疼痛的神经瘤是周围神经性疼痛的主要来源，并且最近的数据越来越多地指出免疫细胞和神经胶质细胞是疼痛的驱动因素，这些信号分子是它们产生对受伤的神经元作用的作用，生成的数据实际上可以提供重要而新颖的见解患者的神经性疼痛的病理生理学又可能导致新的治疗策略。可以想象的数据可能会揭示疼痛的驱动因素可能会随着时间而变化并且可能与患者或共存疾病的基因型有关，临床前研究的特征将不会揭示。