Neural Mechanisms Underlying IC/BPS

IC/BPS 背后的神经机制

• 批准号: 10182438
• 负责人: Vijay K Samineni
• 金额: $ 46.94万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-05 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10182438
• 关键词: Absence of pain sensation; Affect; Analgesics; Behavioral; Bladder; Bladder Control; Bladder Diseases; Brain Stem; Cells; Chronic; Clinical; Cystitis; Development; Electric Stimulation; Electrophysiology (science); Equilibrium; Equipment and supply inventories; Etiology; Exhibits; Functional disorder; Genetic; Hypersensitivity; Interstitial Cystitis; Knowledge; Lead; Local Therapy; Maintenance; Molecular; Morphine; Mus; Neuraxis; Neurons; Neurotransmitters; Nociception; Opioid; Output; Pain; Pathology; Pathway interactions; Pelvic Pain; Peripheral; Persistent pain; Pharmaceutical Preparations; Pharmacology; Population; Process; Property; Regulation; Resolution; Role; Slice; Spinal; Spinal Cord; Stimulus; Symptoms; Synapses; Syndrome; System; Testing; Therapeutic; United States; Woman; Work; afferent nerve; anatomical tracing; base; bladder pain; chronic pain; design; in vivo calcium imaging; insight; mouse model; neural circuit; neuromechanism; neuronal circuitry; optogenetics; pain processing; receptor; response; therapeutic target; therapy development; transcriptome sequencing; transcriptomics; transmission process

Abstract Interstitial cystitis/bladder pain syndromes (IC/BPS) is a debilitating condition with loss of bladder control and severe bladder pain on bladder filling. Mechanisms underlying IC/BPS are poorly understood. Compelling studies show that the brainstem via direct projection to the spinal cord can directly modulate nociceptive processing and bladder function. In our preliminary studies, we have identified distinct populations of the brainstem neurons that project to the spinal cord. Here we will determine the precise roles of these distinct brainstem neurons in the pathology of IC/BPS. We will determine if IC/BPS leads to maladaptive changes in these distinct populations. We will use optogenetics, anatomical tracing, in vivo calcium imaging, slice electrophysiology and RNA sequencing to determine if IC/BPS leads to functional changes at the cellular and systems level in these circuits. Do these changes drive IC/BPS? Does reversing these maladaptive changes relieve IC/BPS? Together, this work will reveal the specific roles for this neural circuits in IC/BPS. This rich information can have broad implications for potential new direction in designing safer therapeutic drugs in treatment of the IC/BPS.

摘要 间质性膀胱炎/膀胱疼痛综合征（IC/BPS）是一种使人衰弱的疾病， 膀胱充盈时出现严重膀胱疼痛。IC/BPS的潜在机制知之甚少。令人信服的研究 表明脑干通过直接投射到脊髓可以直接调节伤害性处理， 膀胱功能在我们的初步研究中，我们已经确定了脑干神经元的不同群体， 投射到脊髓。在这里，我们将确定这些不同的脑干神经元的确切作用， IC/BPS的病理学。我们将确定IC/BPS是否导致这些不同人群的适应不良变化。 我们将使用光遗传学、解剖示踪、体内钙成像、切片电生理和RNA 测序以确定IC/BPS是否导致这些回路中细胞和系统水平的功能变化。 这些变化是否推动了IC/BPS？逆转这些适应不良的变化是否能缓解IC/BPS？在一起，这 这项工作将揭示这种神经回路在IC/BPS中的具体作用。这些丰富的信息可以有广泛的 为设计更安全的治疗药物治疗IC/BPS提供了潜在的新方向。