Nociplastic mechanisms in somatic and visceral pain

项目总结/摘要 慢性疼痛是一个重大的社会和经济负担。尽管在过去几年中取得了相当大的进展， 经过几十年的研究，我们对慢性疼痛的神经生物学基础的理解仍然存在， 不完整，这对疼痛管理的改善提出了障碍。多模式调查 慢性疼痛病症内和之间的机制异质性对于开发新的 和有效的精确疼痛治疗。 中枢神经系统（CNS）控制疼痛的感知。中枢神经系统的致敏是一种机制， 假设是慢性疼痛患者中观察到的疼痛和感觉敏感性增加的基础。这 这种机制被称为伤害性疼痛。定量感觉测试（QST），功能磁 磁共振成像（fMRI）和患者报告的结果测量（PROM）是可以使用的方法 共同构建表征个体伤害性的程度和特征的多模态特征， 疼痛表型拟议的F99和K 00项目将使用这些方法来区分收敛和 在诊断上不同的躯体（从骨骼和软组织发出）中， 组织）和内脏（从内部器官发出）慢性疼痛状况。 拟议项目的总体目标是确定共同的和不同的伤害性特征， 躯体和内脏疼痛状况，以最终刺激精确疼痛管理的发展 工具. F99部分的目的是描述伤害性疼痛的感觉和神经生物学特征， 躯体疼痛患者，包括类风湿性关节炎（RA）、骨关节炎（OA）和腕管综合征患者 综合征（CTS），相对于健康对照组和纤维肌痛患者-原型伤害性疼痛 条件这项分析将为这项工作的K 00部分的长期目标奠定基础，其中平行 将在内脏痛患者中评估感觉和神经生物学指标，包括 泌尿系慢性盆腔疼痛综合征（UCPPS）、膀胱过度活动症（OAB）和妇科慢性盆腔疼痛综合征（CPCS） 疼痛（CPP）。来自NIDDK资助的慢性盆腔疼痛研究的多学科方法的数据 （MAPP）研究网络和下尿路功能障碍研究网络（LURN）将被利用 完成K 00项目。总之，F99和K 00工作的指导和研究活动将 为我建立一个职业轨迹，使我成为一个独立的研究人员，在泌尿疼痛的专业知识。

PROJECT SUMMARY/ABSTRACT Chronic pain is a significant social and economic burden. Despite considerable progress over the last several decades of research, our understanding of the neurobiological underpinnings of chronic pain remains incomplete and this presents obstacles for improvement in pain management. Multimodal investigations into the mechanistic heterogeneity within and across chronic pain conditions are critical for the development of new and efficacious precision pain treatments. The central nervous system (CNS) governs the perception of pain. Sensitization of the CNS is a mechanism hypothesized to underly the increased pain and sensory sensitivity observed in patients with chronic pain. This mechanism is referred to as nociplastic pain. Quantitative sensory testing (QST), functional magnetic resonance imaging (fMRI), and patient-reported outcome measures (PROMs) are methods that can be used together to build multimodal profiles that characterize the degree and features of an individual’s nociplastic pain phenotype. The proposed F99 and K00 projects will use these methods to distinguish convergent and divergent nociplastic mechanisms across diagnostically distinct somatic (emanating from bones and soft tissue) and visceral (emanating from internal organs) chronic pain conditions. The overall objective for the proposed project is to identify shared and distinct nociplastic profiles between somatic and visceral pain conditions to ultimately stimulate the development of precision pain management tools. The goal of the F99 portion is to characterize sensory and neurobiological features of nociplastic pain in patients with somatic pain, including those with rheumatoid arthritis (RA), osteoarthritis (OA), and carpal tunnel syndrome (CTS), relative to healthy controls and patients with fibromyalgia – the archetypal nociplastic pain condition. This analysis will build a foundation for the long-term aim of this work’s K00 portion, where parallel sensory and neurobiological measures will be assessed in patients with visceral pain, including those with urologic chronic pelvic pain syndrome (UCPPS), overactive bladder (OAB), and gynecological chronic pelvic pain (CPP). Data from the NIDDK-funded Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network and Lower Urinary Tract Dysfunction Research Network (LURN) will be leveraged to complete the K00 project. Together, the mentoring and research activities of this F99 and K00 work will establish a career trajectory for me to become an independent researcher with expertise in urological pain.