Cross Organ Mechanisms in Chronic Pelvic Pain

慢性盆腔疼痛的跨器官机制

基本信息

批准号：
10656603
负责人：
Frank Fu-sheng Tu
金额：
$ 72.35万
依托单位：
NORTHSHORE UNIVERSITY HEALTHSYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-15 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10656603
关键词：
Acceleration Accounting Acute Address Afferent Neurons Animals Anti-Inflammatory Agents Biological Biological Assay Bladder Blood Brain Chronic Clinical Collection Communication Data Development Distress Dysmenorrhea Early Intervention Electroencephalography Equipment and supply inventories Event Event-Related Potentials Exhibits Follow-Up Studies Functional disorder Health Home Hypersensitivity Impairment Inflammation Inflammatory Inflammatory Response Interstitial Cystitis Irritable Bowel Syndrome Knowledge Leukocytes Longitudinal Studies Longitudinal, observational study Measurement Measures Mediating Methods Mission Natural History Neurobiology Neurologic Non-Visceral Organ Outcome Pain Pain Disorder Pain Free Participant Pathway interactions Patients Pelvic Pain Pelvis Perception Persons Phenotype Pilot Projects Populations at Risk Prevention Prevention strategy Prospective Studies Psychophysics Quality of life Questionnaires Recording of previous events Risk Sampling Sensory Severities Spinal Symptoms System TLR4 gene Testing Time United States National Institutes of Health Vertebral column Visceral Whole Blood Woman aged bladder pain care costs chronic pain chronic pain patient chronic painful condition chronic pelvic pain cohort cost density effective therapy endometriosis experience follow-up health assessment high risk innovation mindfulness meditation multimodality neural neuromechanism pain chronification pain outcome pain sensitivity pain symptom predicting response prevent productivity loss prospective psychologic public health priorities reproductive response screening symptomatology systemic inflammatory response two-dimensional virtual young woman

项目摘要

Chronic pelvic pain (CPP) disorders cause significant distress and often lack effective treatments. Although dysmenorrhea is closely associated with 80% of cases of CPP, little is known about why only some women with menstrual pain go on to develop conditions like interstitial cystitis/bladder pain syndrome, irritable bowel syndrome, or endometriosis. Intriguingly, 20% of dysmenorrhea sufferers (without chronic pain) display a key feature of many CPP states, bladder hypersensitivity on noninvasive bladder filling, and appear on pilot studies at higher risk of CPP in one year. In this team’s prior studies, women with the dysmenorrhea with bladder pain phenotype (DYSB) also exhibit greater somatic symptom burden, experimental pain hypersensitivity, and psychological dysregulation—features found in many chronic pain patients. As little is known about the acute to CPP transition, this renewal application seeks to track pelvic pain symptomatology prospectively in DYSB women and to expand those initial mechanistic studies. Aim 1 is a two-year longitudinal study of 1050 young women oversampled for dysmenorrhea to find 150 DYSB cases and establish their risk trajectory for CPP symptoms vs. those with only dysmenorrhea (DYS only = 750) and healthy controls (HC = 150). Along with a virtual bladder filling screening test, other patient health factors potentially predicting development of CPP will be captured, including overall pelvic experiences and general sensory sensitivity. Aim 2 will investigate 100 DYSB and 100 controls (DYS only and HC) on two dimensions of CPP mechanistically—bladder hypersensitivity and multimodal hypersensitivity (a composite of experimentally evoked responses to nonvisceral quantitative sensory tests [QST]). Electroencephalography-based studies will further investigate which neurological mechanisms (i.e. ascending neural hyperexcitability, descending inhibition, and neural oscillations) underlie these two components and predict one-year worsening of CPP symptoms. Aim 3 studies whether another key mechanism of pain sensitization, Toll-like Receptor-4 inflammatory reactivity, influences CPP progression, using an integrated whole-blood collection and leukocyte culture system. This renewal application significantly extends this discovery of an at-risk phenotype by providing a method for expanding screening and characterizing reversible mechanisms. This essential followup study utilizes innovative combinations of QST with EEG measurements of brain activity to identify the mechanisms responsible for CPP-related-sensory abnormalities, alongside measures of systemic inflammatory reactivity that are strongly implicated in sensory hypersensitivity. Notably, if these are confirmed, candidate early interventions already exist to modulate these mechanisms, including mindfulness meditation and consistent anti-inflammatory use for dysmenorrhea. Successful completion of these studies would accelerate efforts to prevent the transition from acute to chronic pelvic pain, a major public health priority.

慢性盆腔疼痛 (CPP) 疾病会导致严重的痛苦，并且往往缺乏有效的治疗方法。痛经与 80% 的 CPP 病例密切相关，但为何只有部分女性患有痛经却知之甚少月经疼痛会导致间质性膀胱炎/膀胱疼痛综合征、肠易激等病症有趣的是，20% 的痛经患者（无慢性疼痛）表现出关键症状。许多 CPP 状态的特征，膀胱对无创膀胱充盈过敏，并出现在试点研究中在该团队之前的研究中，患有痛经并伴有膀胱疼痛的女性在一年内患 CPP 的风险更高。表型（DYSB）还表现出更大的躯体症状负担、实验性疼痛超敏反应和心理失调——在许多慢性疼痛患者中发现的特征，因为人们对急性疼痛知之甚少。 CPP 过渡，此更新应用程序旨在前瞻性地跟踪 DYSB 中的盆腔疼痛症状目标 1 是一项针对 1050 名年轻人的为期两年的纵向研究。对患有痛经的女性进行过采样，发现 150 例 DYSB 病例，并确定她们患 CPP 的风险轨迹症状与仅痛经的患者（仅 DYS = 750）和健康对照者（HC = 150）的比较。虚拟膀胱充盈筛查测试，其他可能预测 CPP 发展的患者健康因素将目标 2 将调查 100 个人，包括整体骨盆体验和一般感官敏感性。 DYSB 和 100 在 CPP 机械二维上进行控制（仅限 DYS 和 HC）——膀胱超敏反应和多模式超敏反应（实验诱发反应的复合体）基于脑电图的非内脏定量感觉测试[QST]）将进一步调查。哪些神经机制（即上行神经过度兴奋、下行抑制和神经振荡）是这两个组成部分的基础，并预测目标 3 研究中 CPP 症状一年内会恶化。疼痛敏化的另一个关键机制 Toll 样受体 4 炎症反应性是否会影响 CPP 进展，使用集成的全血采集和白细胞培养系统。通过提供一种方法，该应用显着扩展了对危险表型的发现这项重要的后续研究利用了扩展可逆机制的筛选和表征。 QST 与脑电图测量大脑活动的创新组合以确定其机制与 CPP 相关的感觉异常以及全身炎症反应有关值得注意的是，如果这些被证实，则与感觉超敏反应密切相关。候选早期干预措施已经存在来调节这些机制，包括正念冥想持续使用抗炎药治疗痛经将有助于成功完成这些研究。加快努力防止急性盆腔疼痛向慢性盆腔疼痛的转变，这是一项重要的公共卫生优先事项。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Bladder Pain Sensitivity Is a Potential Risk Factor for Irritable Bowel Syndrome.

膀胱疼痛敏感性是肠易激综合症的潜在危险因素。

DOI：
发表时间：
2023-07
期刊：
影响因子：
3.1
作者：
Shlobin, Arielle E;Tu, Frank F;Sain, Cody R;Kmiecik, Matthew J;Kantarovich, Diana;Singh, Lavisha;Wang, Chi E;Hellman, Kevin M
通讯作者：
Hellman, Kevin M

Somatic symptoms in women with dysmenorrhea and noncyclic pelvic pain.

患有痛经和非周期性盆腔疼痛的女性的躯体症状。

DOI：
发表时间：
2018-10
期刊：
影响因子：
0
作者：
Zuckerman, Rebecca M;Silton, Rebecca L;Tu, Frank F;Eng, Joshua S;Hellman, Kevin M
通讯作者：
Hellman, Kevin M

Dysmenorrhea and Endometriosis in the Adolescent

青少年痛经和子宫内膜异位症

DOI：
发表时间：
1970-01-01
期刊：
2015 IEEE 4th Global Conference on Consumer Electronics (GCCE)
影响因子：
0
作者：
Karen Gerancher
通讯作者：
Karen Gerancher

Cortical Mechanisms of Visual Hypersensitivity in Women at Risk for Chronic Pelvic Pain.

有慢性盆腔疼痛风险的女性视觉过敏的皮质机制。

DOI：
发表时间：
2021-01-18
期刊：
影响因子：
0
作者：
Kmiecik, Matthew J;Tu, Frank F;Silton, Rebecca L;Dillane, Katlyn E;Roth, Genevieve E;Harte, Steven E;Hellman, Kevin M
通讯作者：
Hellman, Kevin M

Clinical profile of comorbid dysmenorrhea and bladder sensitivity: a cross-sectional analysis.

共病痛经和膀胱敏感性的临床特征：横断面分析。

DOI：
发表时间：
2020
期刊：
影响因子：
9.8
作者：
Tu, Frank F;Datta, Avisek;Atashroo, Diana;Senapati, Sangeeta;Roth, Genevieve;Clauw, Daniel J;Hellman, Kevin M
通讯作者：
Hellman, Kevin M