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.

项目摘要 非神经发生过度活跃的膀胱（OAB）（即尿液紧急，有或没有紧急尿失禁， 频率和夜尿）影响了7种美国男女。可能很难有效治疗，现在 方法是千篇一律的，反复试验，这在很大程度上是因为OAB的病因尚不清楚。一个 动物和离体研究的实质性体系暗示传入活性增加并改变了中枢神经系统 OAB病理生理学中兴奋性信号的处理，导致膀胱超敏反应。然而， 可能反映出膀胱超敏反应状态的临床特征很识别，因此 基于传入的病理生理机制的表型OAB，这对于个性化至关重要 OAB护理仍然难以捉摸。作为回应，我们假设中央敏化（CS）是一个 某些人的OAB基础的病理生理机制，这可能解释了膀胱 OAB中提出的高敏性。我们的初步工作的发现证明了较高的时间 疼痛的求和（即用定量感觉测试索引的CS的主要标记，TSP） 患者似乎支持这一点。但是，我们仍然对CS在OAB中的表现一无所知，包括如何 相关的可能是OAB男性。因此，我们现在建议CS不仅有助于膀胱 敏感性，但也对社会心理负担，特别是增加了负面影响（这是一个常见的发现 两个患有CS介导的人和OAB），然后影响膀胱症状。我们将测试这个 假设有200个具有OAB和60个非OAB对照的男性和女性的样本，并使用高度创新的， 跨学科方法。 AIM 1标识了OAB中CS的表型特征，包括更大 中央感官敏感性，心理社会因素升高，慢性疼痛条件的合并症以及更大的 尿症状。因为CS链接到OAB以前从未在男性中进行检查，所以我们将测试性别 CS相关表型的差异。 AIM 2将首次直接测试CS对膀胱的影响 OAB的灵敏度。 AIM 3将检查CS是否适应日常的负面情感影响 使用最先进的生态瞬时评估方法的OAB症状。完成后，我们 希望能够识别具有基于机制的表型（CS相关的OAB）的OAB个体 首次通过签名机械和表型特征。我们预计与此CS的个人 OAB关联可能是由于高思想的影响和CS介导的超敏反应，将会更多 使用标准OAB干预措施（即OAB药物）难以治疗，可能需要多模式或 晚期治疗。这将通过未来的干预研究来评估以衡量个性化的OAB 基于基本CS机制的治疗结果，并确定这种OAB-CS关联的因果关系， 这将有助于迎来精确医学时代，以优化对OAB的男性和女性的护理。