Human Tissue Procurement and Processing Core

项目摘要(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取得了进展，但小鼠的疼痛靶点已经经历了 几十年来，在为慢性疼痛患者转换为新的有效和安全的治疗方法方面遇到了困难。匮乏 老鼠和人类疼痛治疗之间的转换突显了疼痛动物模型的局限性。 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 在疼痛生物学方面取得重要的新进展，改善临床翻译的机会。《人类》 组织采购和处理核心将负责从尸检中获得高质量的组织 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性感受器的异常放电，其 胞体位于背根神经节或三叉神经节。这些神经节位于中枢神经之外。 如果它们能被选择性地抑制，将成为理想的疼痛治疗靶点。因此，我们建议 从尸检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计划。这项IRB批准的协议已经 正在进行中，并从25名捐赠者那里收集了样本，其中一些样本已成功处理用于 单核基因组分析。中心将在这些已建立的组织采购和加工的基础上再接再厉 与其他U19中心合作的协议。 为了描述慢性疼痛患者的分子变化，慢性幻肢患者 继发于症状性神经瘤的神经瘤将在肌肉神经再支配手术中获得。 该协议已获得IRB批准，并已在注册中。新鲜和冷冻的样品将提供给中心 单细胞基因组分析的研究人员。 核心中心还将维持一个已确认冰冻组织的组织库，以便分发给中心调查人员 以及精准人类痛苦网络的调查人员。

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.