Identification of pain inducing tissue components in lipedema patients

脂肪水肿是一种病因不明的严重疾病，约占所有女性的7%。它伴随着难以治疗的疼痛，加重了其强大的心理负担。本项目的目的是确定1） 影响患者的感觉方式，2） 患者组织中的炎症介质和生长因子改变，3） 新的患者组织因子修饰培养的伤害感受器，4） 培养的伤害感受神经元如何被鉴定的改变的候选患者组织因子功能性地修饰，5） 如果这些变化保留在来自诱导多能干细胞的人类伤害感受器中，6） 如何应对这些变化。我们的目标是确定病理生理学机制，使用患者的定量感觉测试，BioPlex200组织分析患者组织，伤害感受器培养物的高含量筛选显微镜，功能分析基于“信号指纹”的HCS显微镜，转录组分析和药理学干扰啮齿动物伤害感受器以及人类诱导多能干细胞（hiPSC）衍生的伤害感受器，和动物行为实验。了解脂肪水肿疼痛的细胞机制为改善疼痛治疗减少患者痛苦的漫长道路奠定了基础。

Lipedema is a severe disease of unknown etiology affecting estimated 7% of all women. It is accompanied by ill-treatable pain aggravating its strong psychosocial burden. Aim of this project is to determine1) the sensory modalities affected in patients,2) the inflammatory mediators and growth factors altered in patients’ tissue,3) which novel patient tissue factors modify cultured nociceptors, 4) how cultured nociceptive neurons are functionally modified by the identified altered candidate patient tissue factors,5) if those changes are preserved in human nociceptors derived from induced pluripotent stem cells,6) how these changes can pharmacologically mitigated. We aim to identify pathophysiological mechanisms using Quantitative Sensory Testing of patients, BioPlex200 Tissue analysis of patient tissue, High Content Screening microscopy of nociceptor cultures, functional analysis by HCS-microscopy based “signaling fingerprinting”, transcriptome analysis, and pharmacological interference on rodent nociceptors as well as on human induced pluripotent stem cell (hiPSC) derived nociceptors, and animal behavioral experiments. Understanding cellular mechanisms underlying lipedema pain creates the basis for the long path toward improvement of pain therapeutic reduction of patients suffering.