CNS Mechanisms of IC/BPS

IC/BPS 的 CNS 机制

• 批准号: 9753224
• 负责人: Robert W Gereau
• 金额: $ 57.04万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9753224
• 关键词: Acute Cystitis; Address; Affect; Affective; Amygdaloid structure; Anatomy; Animals; Anxiety; Behavior; Bladder; Brain; Brain Stem; Cell Nucleus; Cells; Chronic; Clinical; Clinical Research; Comorbidity; Cystitis; Data; Development; Disease; Electrophysiology (science); Etiology; Exhibits; Functional Imaging; Functional disorder; Future; Genetic; Hypersensitivity; Image; Increased frequency of micturition; Injury; Interstitial Cystitis; Lead; Maps; Mediating; Mediator of activation protein; Mental Depression; Modeling; Molecular; Monitor; Mood Disorders; Mus; Neurons; Neurosciences; Nociception; Pain; Pathology; Patients; Persistent pain; Population; Prevalence; Process; Publishing; Quality of life; Rattus; Resolution; Role; Series; Slice; Structure; Symptoms; Synapses; Technology; Testing; Time; United States; Viral; Wireless Technology; Woman; Work; awake; base; bladder pain; central sensitization; chronic pain; chronic pelvic pain; design; effective therapy; imaging study; in vivo; in vivo imaging; inflammatory pain; insight; interdisciplinary approach; micturition urgency; mouse model; negative affect; neural circuit; neuronal circuitry; optogenetics; pain reduction; pre-clinical; relating to nervous system; sensor; spontaneous pain; urologic

Abstract Interstitial cystitis/Bladder Pain Syndrome (IC/BPS) is a serious and painful condition of unknown etiology that affects 3-6% of women in the United States. The major clinical symptoms of IC/BPS are pain on bladder filling and increased urinary urgency and frequency. The majority of IC/BPS patients (90%) also suffer from comorbid anxiety and/or depression, contributing to a poor quality of life. The high rate of comorbid affective disorders in IC/BPS patients suggests that a common supraspinal neural circuit may be responsible for both enhanced pain and negative affect in patients with IC/BPS. Based on a large body of work in the neurosciences, we hypothesize that the central nucleus of the amygdala (CeA) is a crucial hub of neuronal activity that regulates both bladder pain and negative affect. In this project, we propose a series of studies that seeks to determine the necessity and sufficiency of neuronal subpopulations in the CeA in the induction of voiding dysfunction, pain sensitization, and comorbid anxiety and depression in models of cystitis. Does activation of this circuit lead only to hypersensitivity to stimulation, or is this also critical for ongoing or spontaneous pain? Does the same population of neurons mediate both pain sensitization and increased anxiety following injury? What are the critical inputs and projections from these neurons that lead to these debilitating consequences of cystitis? We employ a multidisciplinary approach including viral anatomical tract tracing, optogenetics, chemogenetics, and in vivo imaging of neural activity in awake, freely moving mice to address these questions. These studies will provide new insights into the critical role of the CeA in bladder pain and comorbid affective disorders in the context of bladder pain syndrome, and provide the basis for future studies building on this to gain insights into circuit, cellular and synaptic mechanisms of voiding dysfunction, chronic pain and comorbid anxiety and depression.

摘要