Coordination Funds

神经性疼痛的消退和恢复是依赖于诸如炎症消退和神经元通路恢复的机制的主动过程。神经损伤引起的疼痛可能会在没有完全的解剖学和生理学恢复的情况下消退，这一事实表明这是一个严格调节的过程。如果这种自我愈合过程受到干扰，慢性疼痛可能随之而来，例如慢性术后疼痛。研究这个问题，为什么尽管有持续的神经功能缺损，但神经损伤后疼痛在一些患者中消失，为什么慢性术后疼痛在一些患者中消退，而在另一些患者中仍然存在，这将使我们更接近有针对性的有效治疗。在这里，我们的目的是调查恢复模式和机制的疼痛决议在外周躯体感觉系统。我们将利用涉及临床，临床前和基础科学的综合转化方法，以及对外周过程的CNS控制的试点研究。临床研究单位“疼痛的外周机制及其解决方案”（ResolvePAIN）将使用以患者为中心的自上而下的方法和自下而上的方法，包括细胞模型、涉及苍蝇和啮齿动物的模型生物体，进行多层次的联合研究。临床模型疾病都有一个共同的特点，即在一些患者中出现恢复，但不是所有患者。我们将采用横断面和纵向设计，对手术/创伤、化疗、自身免疫和遗传性疾病后的神经性疼痛状态患者进行临床表型和随访。我们将建立人类神经和背根神经节成像（MR神经成像），皮肤和血液生物材料分析的创新方法的核心单元，使用统一的数据库，以确定疾病亚组和疼痛解决的临床模式。将采用三种匹配的临床前分辨率模型，创伤性神经损伤，自身抗体转移和化疗诱导的神经病变，以及神经元/非神经元细胞系统和果蝇中的分辨率范例。我们将使用有针对性和无偏见的方法相结合的特点外周机械疼痛模式和网络及其解决方案。靶点涉及神经炎症、离子通道功能、细胞-细胞接触、神经营养因子和神经元引导因子、氧化脂质、遗传学和表观遗传学以及外周CNS控制，如疼痛的社会维度所示。为了可持续地实现这一目标，ResolvePain将在维尔茨堡的“综合临床医生科学家学院”的疼痛课程中培养麻醉学，神经病学，神经放射学，神经外科，外科和内科的新一代临床医生科学家的临床和科学教育。了解神经性疼痛状态的恢复将有助于确定有风险的患者亚组，并需要个性化的强化治疗和新的分子治疗靶点，以促进神经性疼痛状态的恢复。

Resolution of and recovery from neuropathic pain are active processes which depend on mechanisms such as resolution of inflammation and restoration of neuronal pathways. The fact that pain from a nerve lesion may subside without complete anatomical and physiological recovery indicates that this is a tightly regulated process. If this self-healing process is disturbed, chronic pain may ensue, e.g. chronic postoperative pain. Answering the question, why pain resolves in some patients after a nerve lesion despite persistent neurological deficits, and why chronic postoperative pain subsides in some and remains in others, will bring us closer to targeted efficient treatments. Here, we aim to investigate recovery patterns and mechanisms of pain resolution in the peripheral somatosensory system. We will utilize a combined translational approach involving clinical, preclinical, and basic sciences as well as pilot studies on CNS control over the peripheral processes. The Clinical Research Unit “Peripheral mechanisms of pain and their resolution” (ResolvePAIN) will use a top-down approach centered around patients and a bottom-up approach including cellular models, model organisms involving flies and rodents in a combined multi-level effort. The clinical model diseases all share the hallmark that recovery occurs in some patients but not in all. We will use a cross-sectional and longitudinal design to clinically phenotype and follow up patients with neuropathic pain states after surgery/trauma, chemotherapy, autoimmunity and in a genetic disease. We will set up core units for innovative methods of human nerve and dorsal-root-ganglion imaging (MR Neurography), skin and blood biomaterial analysis, using a uniform database, to identify disease subgroups and clinical patterns of pain resolution. Three matched preclinical resolution models, traumatic nerve injury, autoantibody transfer- and chemotherapy-induced neuropathy, as well as resolution paradigms in neuronal/non-neuronal cellular systems and flies will be employed. We will characterize peripheral mechanistic pain patterns and networks and their resolution using a combination of targeted and unbiased approaches. Targets involve neuroinflammation, ion channel function, cell-cell contacts, neurotrophic and neuronal guidance factors, oxidized lipids, genetics and epigenetics as well as CNS control of the periphery as exemplified in the social dimension of pain. To reach this end sustainably, ResolvePAIN will foster clinical and scientific education of a new generation of Clinician Scientists in anesthesiology, neurology, neuroradiology, neurosurgery, surgery, and internal medicine in a pain class of the "Integrative Clinician Scientists College" Würzburg. Understanding recovery from neuropathic pain states will help to identify subgroups of patients at risk and in need of personalized intensified treatment and new molecular treatment targets to promote recovery in neuropathic pain states.