ICECAN

ICECAN

• 批准号: 8964375
• 负责人: Thomas C. Chelimsky
• 金额: $ 66.98万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8964375
• 关键词: Address; Adrenergic beta-Antagonists; Affect; American; Area; Autonomic nervous system; Autonomic nervous system disorders; Baroreflex; Bladder; Blood; Blood Pressure; Brain; Brain Stem; Brain imaging; Bystander Effect; Characteristics; Clinical; Comorbidity; Complex; Congenital neurologic anomalies; Crossover Design; Data; Disease; Disease Marker; Employment; Enrollment; Epigenetic Process; Etiology; Frequencies; Functional disorder; Funding; Future; Genes; Grant; Health; Heart Rate; Human; Hypertrophy; Impairment; Interstitial Cystitis; Investigation; Lead; Link; Measurement; Measures; Medial; Minority; Modification; Molecular; Monitor; Morphology; Nervous System Physiology; Outcome; Pain; Pain management; Pathway interactions; Patients; Pelvic Pain; Pharmaceutical Preparations; Phenotype; Physiology; Placebos; Population; Prefrontal Cortex; Prevalence; Prospective Studies; Psychology; RNA; Research; Science; Scientist; Site; Sleep Deprivation; Staging; Symptoms; Syndrome; System; United States National Institutes of Health; Visceral pain; Woman; base; brain pathway; chronic pain; chronic pelvic pain; cohort; cost; economic cost; effective therapy; flexibility; frontal lobe; heart rate variability; improved; indexing; innovation; insight; longitudinal design; midbrain central gray substance; morphometry; neural circuit; neuroimaging; novel strategies; public health relevance; relating to nervous system; response; skills; standard care

 DESCRIPTION (provided by applicant): Despite 25 years of NIH funded investigation on interstitial cystitis/bladder pain syndrome (IC/BPS) focused on the bladder, no meaningful new therapies have emerged and the pathophysiology remains obscure. IC/BPS afflicts 3 to 8 million women in the US with chronic pain, voiding dysfunction, sleep deprivation and other co- morbid conditions that interfere with relationships and employment at a cost of over $100M/yr. We have assembled a unique group of accomplished clinicians and scientists with diverse expertise that spans clinical pelvic pain, neuroimaging, brainstem connectivity, pain modulation, autonomic disorders and heart rate variability across 3 sites. Based on the first cycle findings of the ICEPAC study (Interstitial Cystitis - Elucidation of Psychophysiologic and Autonomic Characteristics), this innovative proposal aims to understand whether correcting autonomic nervous system abnormalities and the underlying brain pathways can change the course of chronic pelvic pain in women suffering from IC/BPS and myofascial pelvic pain syndrome (MPP). Prior findings from ICEPAC showed that these two disorders differ in their physiology and psychology. Yet, they are often confused clinically. ICEPAC found that the majority of women have both disorders together, while a large minority has one. Careful phenotyping, however, demonstrates a unique autonomic profile for IC/BPS, with reduced autonomic nervous system responsiveness (ANS-R) measured by heart rate variability. The current proposal therefore aims to determine if ANS-R impairment may cause IC/BPS and its symptoms. The first aim will assess whether changes in ANS-R precede or follow changes in disease state over 24 weeks in subjects with IC/BPS and MPP. The second aim will evaluate how the disease state responds to direct modification of ANS-R using a medication intended to improve ANS-R by reducing sympathetic tone (the beta-blocker metroprolol vs placebo). We expect better ANS-R to improve response of IC/BPS more than it improves response of MPP to standard treatments. The third aim will determine whether ANS-R changes are reflected in connectivity between a high level control area in the brain, the prefrontal cortex, and the periaqueductal gray, a brainstem switch that controls pain and autonomic functions including blood pressure, heart rate and bladder function. We expect that stronger connections will reflect higher ANS-R when IC/BPS improves. This proposal is innovative in that 1) we are the first group to rigorously parse the phenotypes of IC/BPS and MPP, enabling assessment of specific disease markers; and 2) this is the first longitudinal prospective study assessing ANS-R in any type of chronic pain to assess possible causality. Findings from this study may provide entirely new insight into the relationship of autonomic and pain pathways. If the hypothesis that poor ANS-R may cause or maintain chronic pain states proves correct, entirely new avenues of chronic pain treatment may open, not just in chronic pelvic pain, but in other types of pain as well. Importantly, we would gain completely new insight into the interaction between these very complex neural systems.

 描述（由申请人提供）：尽管 25 年来 NIH 资助了针对膀胱的间质性膀胱炎/膀胱疼痛综合征 (IC/BPS) 的研究，但尚未出现有意义的新疗法，并且病理生理学仍然不清楚。 IC/BPS 困扰着美国 3 至 800 万女性，她们患有慢性疼痛、排尿功能障碍、睡眠不足和其他影响人际关系和就业的共病，每年造成的损失超过 1 亿美元。我们组建了一支独特的团队，由经验丰富的临床医生和科学家组成，他们拥有不同的专业知识，涵盖三个站点的临床骨盆疼痛、神经影像学、脑干连接、疼痛调节、自主神经紊乱和心率变异性。基于 ICEPAC 研究（间质性膀胱炎 - 阐明心理生理和自主神经特征）的第一轮研究结果，这一创新提案旨在了解纠正自主神经系统异常和潜在的大脑通路是否可以改变患有 IC/BPS 和肌筋膜骨盆疼痛综合征 (MPP) 的女性慢性盆腔疼痛的病程。 ICEPAC 先前的研究结果表明，这两种疾病在生理和心理上有所不同。然而，它们在临床上经常被混淆。 ICEPAC 发现，大多数女性同时患有这两种疾病，而极少数女性同时患有一种疾病。然而，仔细的表型分析表明 IC/BPS 具有独特的自主神经特征，通过心率变异性测量自主神经系统反应性 (ANS-R) 降低。因此，当前提案旨在确定 ANS-R 损伤是否可能导致 IC/BPS 及其症状。第一个目标是评估 IC/BPS 和 MPP 受试者 24 周内 ANS-R 的变化是先于还是随后发生疾病状态变化。第二个目标是评估疾病状态对使用旨在通过降低交感神经紧张来改善 ANS-R 的药物（β 受体阻滞剂美托洛尔与安慰剂）直接修改 ANS-R 的反应。我们期望更好的 ANS-R 能够改善 IC/BPS 的反应，而不是改善 MPP 对标准治疗的反应。第三个目标将确定 ANS-R 的变化是否反映在大脑高级控制区域、前额皮质和导水管周围灰质之间的连接性上，导水管周围灰质是控制疼痛和自主功能（包括血压、心率和膀胱功能）的脑干开关。我们预计，当 IC/BPS 改善时，更强的连接将反映更高的 ANS-R。该提案的创新之处在于：1）我们是第一个严格解析IC/BPS和MPP表型的小组，从而能够评估特定的疾病标志物； 2) 这是第一个纵向前瞻性研究，评估 ANS-R 在任何类型的慢性疼痛中的作用，以评估可能的因果关系。这项研究的结果可能为自主神经和疼痛通路的关系提供全新的见解。如果 ANS-R 不良可能导致或维持慢性疼痛状态的假设被证明是正确的，那么慢性疼痛治疗的全新途径可能会开辟，不仅可以治疗慢性盆腔疼痛，还可以治疗其他类型的疼痛。重要的是，我们将对这些非常复杂的神经系统之间的相互作用获得全新的见解。