Harvard PRECISION Human Pain Center

项目总结(总体) 慢性疼痛每年影响2500万美国人，对生活质量和 生产力。尽管我们在动物模型中对伤害性感受的理解取得了进展，但新的和有效的 对慢性疼痛患者的治疗一直缺乏。老鼠和人之间的糟糕翻译 疼痛靶标突显了疼痛动物模型的局限性。单细胞基因组学与人类基因组学研究进展 生理学直接在人体组织部位疼痛研究人员取得重要新进展与改进 临床翻译的机会。哈佛精密人类疼痛中心建议利用国家- 最先进的单细胞技术表征人类伤害性感受器亚型及其基因表达 不同人群的模式不同(项目1)，以及慢性疼痛状况，明显局限于 这些细胞--与痛性神经瘤相关的慢性幻肢痛(项目2)。这些项目将产生 通过与5个核心紧密集成，为科学界提供丰富的数据，这些核心的任务是1)采购高 高质量的人类疼痛相关组织遵循严格的监管实践，2)提供最新的单细胞基因 多组学技术，3)执行先进的单细胞空间转录分析，4)管理， 集成并分发所有数据，以及5)管理并连接到其他精度中心 人类痛苦网络中心。我们中心生成的数据将有助于实现更高的精度 人类疼痛网络，并帮助确定新的疼痛治疗目标并确定其优先顺序，以供未来研究。

PROJECT SUMMARY (Overall) Chronic pain affects >25 million Americans per year, with enormous impacts on both quality of life and productivity. Despite advances in our understanding of nociception in animal models, new and effective treatments for patients with chronic pain have been lacking. The poor translation between mouse and human pain targets has highlighted limitations of animal models of pain. Recent advances in single-cell genomics and physiology directly in human tissue position pain researchers to make important new advances with improved opportunities for clinical translation. The Harvard PRECISION Human Pain Center proposes to leverage state- of-the-art single-cell technologies to characterize human nociceptor subtypes and how their gene expression patterns vary across diverse populations (Project 1) as well as in chronic pain conditions that clearly localize to these cells – chronic phantom limb pain associated with painful neuromas (Project 2). The Projects will generate a wealth of data for the scientific community by closely integrating with 5 Cores tasked with 1) procuring high- quality human pain-related tissues following strict regulatory practices, 2) offering the latest single-cell gene multi-omic technologies, 3) performing advanced single-cell spatial transcriptomic analysis, 4) managing, integrating, and distributing all of the data, and 5) administrating and connecting to Center the other PRECISION Human Pain Network Centers. The data generated by our Center will contribute to this broader PRECISION Human Pain Network and to help identify and prioritizate of novel pain therapeutic targets for future investigation.