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

• 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
• 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

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）是一种 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，而且还对心理社会负担，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 中的敏感性。目标 3 将检验 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来评估，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。