Human Tissue Procurement and Processing Core

项目总结（人体组织采购和处理核心） 尽管我们在动物模型中对伤害性感受的理解有了进步，但小鼠的疼痛靶点经历了 数十年来，我们一直难以将其转化为针对慢性疼痛患者的新型有效和安全的治疗方法。缺乏 小鼠和人类疼痛治疗之间的转换突出了疼痛动物模型的局限性。 将单细胞基因组学和生理学直接应用于人体组织的最新进展使我们的领域定位于 在疼痛生物学方面取得重要的新进展，为临床翻译提供更多机会。人类 组织采购和处理中心将负责从尸检中获得高质量组织 捐赠者和慢性疼痛患者知情同意。 大多数形式的神经性疼痛的经历始于外周伤害感受器的异常放电，其 细胞体位于背根神经节或三叉神经节中。这些神经节位于中枢神经系统之外 如果能选择性地抑制它们，它们将成为理想的疼痛治疗靶点。因此，我们建议， 从死后的人类供体中提取背根神经节、三叉神经节和远端坐骨神经， 在马萨诸塞州总医院建立了快速尸检程序。这个IRB批准的方案已经 目前正在进行中，并已从> 25个捐助者那里收集了样本，其中一些样本已成功处理， 单核基因组测定。核心将建立在这些既定的组织采购和处理基础上 与其他U19中心合作。 为了表征慢性疼痛患者、慢性幻肢患者、 继发于症状性神经瘤的患者将在肌肉神经再支配手术中获得神经瘤。 本方案已获得IRB批准并已入组。将向中心提供新鲜和冷冻样本 单细胞基因组分析的研究人员。 中心还将维持一个组织库，储存去识别的冷冻组织，以分发给中心研究者 和PRECISION人类疼痛网络的研究人员。

PROJECT SUMMARY (Human Tissue Procurement and Processing Core) Despite advances in our understanding of nociception in animal models, pain targets in mice have experienced decades of difficulty in translation to novel effective and safe treatments for patients with chronic pain. The lack of translation between mouse and human pain treatments has highlighted limitations of animal models of pain. Recent advances in applying single-cell genomics and physiology directly to human tissue positions our field to make important new advances in pain biology with improved opportunities for clinical translation. The Human Tissue Procurement and Processing Core will be responsible for obtaining high-quality tissue from post-mortem donors and chronic pain patients with informed consent. The experience of most forms of neuropathic pain begins with abnormal firing of peripheral nociceptors, whose cell bodies are in the dorsal root ganglia or trigeminal ganglia. These ganglia reside outside of the central nervous system and would make ideal pain therapeutic targets if they could be inhibited selectively. We thus propose to extract dorsal root ganglia, trigeminal ganglia and distal sciatic nerve from post-mortem human donors using an established rapid autopsy program at Massachusetts General Hospital. This IRB-approved protocol is already underway and has collected samples from > 25 donors, a selection of which were successfully processed for single-nucleus genomic assays. The Core will build upon these established tissue procurement and processing protocols in collaboration with other U19 Centers. To characterize molecular changes that occur in patients with chronic pain, patients with chronic phantom limb secondary to symptomatic neuromas will have their neuromas procured during muscle reinnervation surgery. This protocol is IRB approved and already enrolling. Fresh and frozen samples will be made available to Center investigators for single-cell genomic assays. The Core will also maintain a tissue bank of deidentified frozen tissues for distribution to Center investigators and investigators across the PRECISION Human Pain Network.