Coordination Funds

协调基金

• 批准号: 400022767
• 负责人: Professor Dr. Martin Schmelz
• 金额: --
• 依托单位: Lehrstuhl für Experimentelle Schmerzforschung
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/400022767?language=en
• 关键词: Coordination; Funds

Chronic pruritus is a highly prevalent cause of suffering and reduced quality of life in patients worldwide, yet our understanding of its basic neurophysiology and of clinically relevant pathomechanisms is limited as are current treatment options. On the other hand, molecular, cellular and even functional characterization of neuronal itch pathways in mice have lifted our understanding of pruritus in this species to a higher level. Our research unit PRUSEARCH set out using this groundbreaking new information from rodents to uncover clinically relevant itch mechanism in patients with inflammatory, neuropathic, and systemic itch. We have established a collaborative multidisciplinary network using basic science methods in a patient-centred approach. Neurophysiologic characterization of pruriceptive and nociceptive sensory neurons in humans and relevant models addresses the translational challenge and optimizes electrical stimulation paradigms for clinical use. Based on comprehensive clinical phenotyping we are characterizing structure-function relations in the different disease entities linking patient reported outcomes to responsiveness to C-fiber specific functional tests, skin expression patterns, innovative structural parameters of epidermal nerve fibers, and central activation patterns in a standardized fashion.While keeping the highly successful basic concept of the first funding period of our research unit, we have decided to advance particularly in our attempt to investigate structure/function relations and strengthen our approaches towards specificity and causality. Key new elements are the inclusion of local external factors (microbiome), characterization of non-myelinating Schwann cells, and generation of functionalized molecularly defined pruriceptors in relevant models. Longitudinal observations will be used to test for the external validity of our functional and structural markers. Thus, we have refined our key objectives from the first funding perioda) Identify crucial mediator systems for inflammatory and non-inflammatory pruritus in chronic itch patients and validate their external validityb) Identify structure/function relations between neuronal and non-neuronal cells that determine itch intensity in chronic pruritusc) Identify common and possibly disparate mechanisms of neuronal sensitization between inflammatory, neuropathic, and systemic itch, but also between in chronic neuropathic itch and pain Thus, our comprehensive approach is intended to clarify the currently unclear overlap between chronic itch and pain conditions and aims for a harmonized diagnostic and therapeutical understanding and procedure. As ultimate objective of our research unit, we expect to uncover clinically relevant pathomechanisms in itch and to develop a comprehensive and mechanism-based diagnostic approach that identifies clinically relevant subgroups of inflammatory, neuropathic, and systemic itch and allows optimization of the specific treatment.

慢性瘙痒症是全球患者痛苦和生活质量降低的一个非常普遍的原因，但我们对其基本神经生理学和临床相关病理机制的理解有限，目前的治疗方案也是如此。另一方面，小鼠神经元瘙痒通路的分子、细胞甚至功能表征将我们对该物种瘙痒的理解提升到了更高的水平。我们的研究单位PRUSESTRUCTURE开始使用来自啮齿动物的这一开创性的新信息，以揭示炎症性、神经性和全身性瘙痒患者的临床相关瘙痒机制。我们建立了一个多学科协作网络，采用以患者为中心的基本科学方法。人类和相关模型中的伤害感受和伤害感受感觉神经元的神经生理学表征解决了翻译挑战并优化了用于临床使用的电刺激范例。基于全面的临床表型，我们正在表征不同疾病实体中的结构-功能关系，将患者报告的结果与对C-纤维特异性功能测试的反应性、皮肤表达模式、表皮神经纤维的创新结构参数以及标准化的中枢激活模式联系起来。在保持我们研究单位第一个资助期非常成功的基本概念的同时，我们已决定特别在研究结构/功能关系的努力中取得进展，并加强我们对特异性和因果关系的研究。关键的新元素包括局部外部因素（微生物组），非髓鞘形成的雪旺细胞的表征，以及在相关模型中产生功能化的分子定义的神经元受体。纵向观察将用于测试我们的功能和结构标记的外部效度。因此，我们从第一个供资期a）开始， 确定慢性瘙痒患者炎性和非炎性瘙痒的关键介质系统，并验证其外部有效性b） 确定神经元和非神经元细胞之间决定慢性瘙痒强度的结构/功能关系c） 识别炎症性、神经性和全身性瘙痒之间以及慢性神经性瘙痒和疼痛之间的神经元致敏的共同和可能不同的机制。因此，我们的综合方法旨在澄清目前尚不清楚的慢性瘙痒和疼痛之间的重叠，并旨在协调诊断和治疗的理解和程序。作为我们研究单位的最终目标，我们期望揭示瘙痒的临床相关病理机制，并开发一种全面的基于机制的诊断方法，该方法可识别炎症性、神经性和全身性瘙痒的临床相关亚组，并优化特定治疗。