Nociplastic mechanisms in somatic and visceral pain

项目摘要/摘要 慢性疼痛是一个重大的社会和经济负担。尽管在过去的几年中取得了相当大的进展 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，这对改善疼痛管理造成了障碍。多式联运调查 慢性疼痛条件内和跨慢性疼痛条件下的机制异质性对于新的 和有效的精确疼痛治疗。 中枢神经系统(CNS)控制着痛觉。中枢神经系统的敏化是一种机制 假设为慢性疼痛患者的疼痛增加和感官敏感性不足。这 发病机制被称为肿瘤性疼痛。功能磁定量感觉测试(QST) 磁共振成像(FMRI)和患者报告的结果测量(PROMS)是可以使用的方法 共同构建多模式配置文件，表征个人的致病程度和特征 疼痛表型。拟议的F99和K00项目将使用这些方法来区分收敛和 在诊断上不同的体细胞(发源于骨骼和软组织)上不同的致癌机制 组织)和内脏(发自内脏)的慢性疼痛状况。 拟议项目的总体目标是确定共同的和不同的肿瘤学特征 躯体和内脏疼痛状况最终刺激精准疼痛管理的发展 工具。F99部分的目标是描述神经瘤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)和腕管患者 综合征(CTS)，相对于健康对照组和纤维肌痛患者--典型的肿瘤性疼痛 条件。这一分析将为这项工作的K00部分的长期目标奠定基础，其中K00部分与 将评估内脏疼痛患者的感觉和神经生物学指标，包括那些 泌尿科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(CPP)。NIDDK资助的慢性盆腔疼痛多学科研究的数据 (MAPP)研究网络和下尿路功能障碍研究网络(Lurn)将被利用 完成K00项目。F99和K00的指导和研究活动将共同努力 为我建立一个职业轨迹，让我成为一名拥有泌尿系统疼痛专业知识的独立研究员。

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.