Central Sensitization and Psychosocial Impacts on Overactive Bladder

膀胱过度活动症的中枢敏化和社会心理影响

基本信息

批准号：
10493272
负责人：
William Stuart Reynolds
金额：
$ 49.59万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-24 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10493272
关键词：
Affect Anger Animals Anxiety Biological Markers Bladder Bladder Control CNS processing Caring Characteristics Chronic Clinical Development Disease Ecological momentary assessment Emotions Esthesia Etiology Event Female Frequencies Functional disorder Future Goals Health Hydration status Hypersensitivity Incontinence Individual Individual Differences Interdisciplinary Study Intervention Intervention Studies Knowledge Link Measures Mediating Mental Depression Modeling Nocturia Oral Outcome Overactive Bladder Pain Pain Research Patients Persons Pharmaceutical Preparations Phenotype Psychology Psychophysics Psychosocial Factor Public Health Research Sampling Sensory Sex Differences Signal Transduction Symptoms Testing Time Treatment outcome Urge Incontinence Urinary Incontinence Urology Woman Work base central sensitization chronic pain chronic painful condition comorbidity diaries improved indexing innovation interdisciplinary approach male men meter micturition urgency multimodality negative affect novel phenotypic biomarker precision medicine prospective psychologic psychosocial response sex societal costs urinary

项目摘要

PROJECT SUMMARY Non-neurogenic overactive bladder (OAB) (i.e. urinary urgency, with or without urgency urinary incontinence, frequency, and nocturia) affects 1 in 7 U.S. men and women. It can be difficult to treat effectively, and the present approach is one-size-fits-all, trial-and-error, in large part because the etiology of OAB remains unclear. A substantive body of animal and ex vivo research implicates increased afferent activity and altered CNS processing of excitatory signals in OAB pathophysiology, contributing to bladder hypersensitivity. However, clinical characteristics that may reflect a bladder hypersensitivity state are poorly recognized and thus phenotyping OAB based on afferent pathophysiologic mechanisms, which would be crucial for individualized OAB care, has remained elusive. In response, we hypothesize that central sensitization (CS) is a pathophysiologic mechanism underlying OAB in certain individuals, which might explain the bladder hypersensitivity proposed in OAB. Findings from our preliminary work demonstrating elevated temporal summation to pain (i.e. primary marker for CS indexed with quantitative sensory testing, TSP) in female OAB patients appear to support this. Yet, we still know very little about how CS manifests in OAB, including how relevant it may be for men with OAB. Therefore, we now propose that CS not only contributes to bladder sensitivity, but also to psychosocial burdens, specifically increased negative affect (which is a frequent finding both individuals with CS-mediated conditions and OAB), which then impacts bladder symptoms. We will test this hypothesis with a sample of 200 men and women with OAB and 60 non-OAB controls, using a highly innovative, interdisciplinary approach. Aim 1 identifies phenotypic features characteristic of CS in OAB, including greater central sensory sensitivity, elevated psychosocial factors, co-morbidity with chronic pain conditions, and greater urinary symptoms. Because CS links to OAB have not previously been examined in men, we will test for sex differences in CS-related phenotypes. Aim 2 will directly test, for the first time, the effects of CS on bladder sensitivity in OAB. Aim 3 will examine whether CS moderates the day-to-day negative affective influences on OAB symptoms using a state-of-the-art ecological momentary assessment approach. When completed, we expect to be able to identify OAB individuals with a mechanism-based phenotype (CS-associated OAB) defined by signature mechanistic and phenotypic features for the first time. We anticipate that individuals with this CS- OAB association, likely because of the high psychosocial impact and CS-mediated hypersensitivity, will be more difficult to treat using standard OAB interventions (i.e. OAB medications) and may require multimodal or advanced therapy. This will be assessed with future intervention studies to measure individualized OAB treatment outcomes based on underlying CS mechanisms and determine causality of this OAB-CS association, which will help usher in an era of precision medicine to optimize care of men and women with OAB.

项目概要非神经源性膀胱过度活动症 (OAB)（即尿急，伴或不伴急迫性尿失禁，尿频和夜尿）影响了七分之一的美国男性和女性。有效治疗比较困难，目前这种方法是一刀切的、反复试验的，很大程度上是因为 OAB 的病因仍不清楚。一个大量动物体和离体研究表明传入活动增加和中枢神经系统改变 OAB 病理生理学中兴奋性信号的处理，导致膀胱过敏。然而，可能反映膀胱过敏状态的临床特征尚未得到充分认识，因此基于传入病理生理机制的 OAB 表型分析，这对于个体化治疗至关重要 OAB 护理，一直难以捉摸。作为回应，我们假设中枢敏化（CS）是某些个体 OAB 的病理生理机制，这可能解释膀胱 OAB 中提出的超敏反应。我们的初步工作结果表明时间升高女性 OAB 的疼痛总和（即以定量感觉测试 (TSP) 为索引的 CS 主要标志物）患者似乎对此表示支持。然而，我们对 CS 在 OAB 中如何体现仍然知之甚少，包括如何这可能与患有 OAB 的男性相关。因此，我们现在提出CS不仅有助于膀胱敏感性，而且还包括社会心理负担，特别是负面情绪的增加（这是一个常见的发现）患有 CS 介导疾病和 OAB 的个体），这会影响膀胱症状。我们将测试这个假设采用高度创新的方法，以 200 名患有 OAB 的男性和女性和 60 名非 OAB 对照为样本，跨学科方法。目标 1 识别 OAB 中 CS 的表型特征，包括更大的中枢感觉敏感性、心理社会因素升高、慢性疼痛的共病以及更大的泌尿系统症状。由于 CS 与 OAB 的联系之前尚未在男性中进行过检查，因此我们将测试性别 CS相关表型的差异。目标 2 将首次直接测试 CS 对膀胱的影响 OAB 的敏感性。目标 3 将检查 CS 是否可以调节日常负面情感影响使用最先进的生态瞬时评估方法来评估 OAB 症状。完成后，我们期望能够识别具有基于机制的表型（CS 相关 OAB）定义的 OAB 个体首次通过特征机制和表型特征。我们预计具有此 CS 的个人 OAB 关联，可能是由于较高的心理社会影响和 CS 介导的超敏反应，将更加使用标准 OAB 干预措施（即 OAB 药物）难以治疗，并且可能需要多模式或先进的疗法。这将通过未来的干预研究进行评估，以测量个体化的 OAB 基于潜在 CS 机制的治疗结果并确定 OAB-CS 关联的因果关系，这将有助于开创精准医疗时代，优化对患有 OAB 的男性和女性的护理。