Coordination Funds

协调基金

• 批准号: 451486974
• 负责人: Professorin Dr. Claudia Sommer
• 金额: --
• 依托单位: Neurologische Klinik und Poliklinik
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/451486974?language=en
• 关键词: Coordination; Funds

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.

神经病理性疼痛的缓解和恢复是活跃的过程，依赖于炎症的缓解和神经元通路的恢复等机制。神经损伤引起的疼痛在没有完全的解剖学和生理学恢复的情况下可能会消退，这一事实表明这是一个严格调控的过程。如果这种自我修复过程被扰乱，可能会接踵而至的慢性疼痛，例如慢性术后疼痛。回答这个问题，为什么一些患者在神经损伤后疼痛消失，尽管存在持续的神经缺陷，以及为什么慢性术后疼痛在一些患者中缓解，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，我们的目标是研究外周躯体感觉系统中疼痛的恢复模式和机制。我们将利用一种综合的翻译方法，包括临床、临床前和基础科学，以及关于中枢神经系统对外周过程控制的初步研究。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等多层次的联合努力。临床模型疾病都有一个共同的特点，即康复发生在一些患者身上，但不是全部。我们将使用横断面和纵向设计，对手术/创伤、化疗、自身免疫和遗传病后神经病理性疼痛状态的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 Neurograph)、皮肤和血液生物材料分析等创新方法的核心单位，使用统一的数据库来识别疾病亚型和疼痛缓解的临床模式。三个匹配的临床前解决模型，创伤性神经损伤，自身抗体转移和化疗引起的神经病，以及神经元/非神经细胞系统和苍蝇的解决范例将被使用。我们将使用有针对性和不偏不倚的方法相结合的方法来描述外周机械性疼痛模式和网络及其解决方案。靶点包括神经炎症、离子通道功能、细胞-细胞接触、神经营养和神经元指导因子、氧化脂质、遗传学和表观遗传学以及中枢神经系统对外周的控制，如社会层面的疼痛。为了可持续地实现这一目标，ResolvePAIN将在维尔茨堡“综合临床科学家学院”的疼痛课程中培养新一代临床科学家在麻醉学、神经学、神经放射学、神经外科、外科和内科方面的临床和科学教育。了解神经病理性疼痛状态的恢复将有助于识别处于危险中的患者亚群，并需要个性化强化治疗和新的分子治疗靶点，以促进神经病理性疼痛状态的恢复。