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

• 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
• 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

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） 我们提出了一个开发人类神经瘤和完整神经组织生物库的计划， 伴随着一套全面的转录组学、蛋白质组学和组织学分析，以生成 疼痛性神经瘤疼痛机制基础的相关性和可检验的假说 可能有助于这种表型的生物化学和信号传导途径，这将是一个重要的工具， 疼痛社区，以确定疼痛神经瘤的确切组成和空间结构， 识别那些只有在疼痛存在时才唯一存在的特征。 鉴于疼痛性神经瘤是周围神经性疼痛的主要来源， 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，因为它们的信号分子， 产生作用于受伤的神经元，所产生的数据可能实际上提供了重要的和新颖的见解， 患者神经病理性疼痛的病理生理学，这反过来又可能导致新的 治疗策略可以想象的是，数据可能会揭示疼痛的驱动因素可能会随着时间的推移而变化 并且可能与患者的基因型或共存疾病有关，这些特征是临床前研究不会发现的。 揭示