Project 2: The cell types and states of painful neuromas

项目总结(项目2) 我们提出了一个计划，建立一个人类神经瘤和完整神经组织的生物库， 伴随着一套全面的转录组、蛋白质组和组织学分析，以产生 痛性神经瘤和活动性神经瘤疼痛发生机制的相关性和可验证性假说 生化和信号通路可能有助于这种表型，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，以及 识别那些仅在存在疼痛的情况下唯一存在的特征。 鉴于痛性神经瘤是周围神经病理性疼痛的主要来源，以及最近的数据 越来越多的人认为免疫细胞和神经胶质细胞是疼痛的驱动力，因为它们所产生的信号分子 产生作用于受损神经元的数据，所产生的数据可能现实地为 神经病理性疼痛的病理生理学转而可能导致新的 治疗策略。可以想象，这些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 并可能与患者的基因或并存疾病有关，这些特征是临床前研究所不具备的 揭晓。

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.