Quantitative Studies of Urinary Bladder Sensation

膀胱感觉的定量研究

• 批准号: 10056956
• 负责人: TIMOTHY J NESS
• 金额: $ 32.67万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-25 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10056956
• 关键词: Acute Pain; Adult; Affect; Afferent Neurons; Agonist; Animal Model; Animals; Back; Basic Science; Biological Models; Bladder; CNS processing; CRF receptor type 2; Caring; Childhood; Clinical; Clinical Data; Corticotropin-Releasing Hormone Receptors; Development; Diagnosis; Disease; Drug Delivery Systems; Drug Industry; Elements; Esthesia; Etiology; Event; Failure; Female; Flare; Functional Imaging; Future; Glutamates; Human; Hypersensitivity; Individual; Inflammation; Inflammatory; Interstitial Cystitis; Lead; Link; Measures; Methodology; Modeling; Molecular; Neonatal; Neural Pathways; Neurons; Nociception; Pain; Pain management; Pathway interactions; Patients; Peptides; Pharmacology; Phenotype; Physiological; Publishing; Rattus; Recurrence; Reflex action; Research; Research Project Grants; Resistance; Rodent; Rodent Model; Role; Secondary to; Sensory; Site; Spinal; Spinal Cord; Stimulus; Stress; Testing; Therapeutic; Therapeutic Agents; Time; Tissues; Toxic effect; Translations; United States; Urinary tract; Urinary tract infection; acute stress; anxiety treatment; bladder pain; chronic pain; clinically relevant; dorsal horn; drug development; experience; improved; innovation; insight; neurochemistry; neuromechanism; neurophysiology; nociceptive response; non-opioid analgesic; noradrenergic; novel; novel therapeutics; opioid epidemic; response; side effect; small molecule

Project Summary/Abstract Acute and chronic pains originating from the urinary bladder are common clinical entities affecting more than 50% of females at some time in their lives. In an attempt to understand urinary bladder hypersensitivity in a translational manner, this ongoing research project has used rodents to define basic neurophysiological elements of bladder sensation at spinal and supraspinal levels. Using urinary bladder distension (UBD)-evoked reflexes and spinal/supraspinal neuronal responses as experimental endpoints, clinically-relevant models of bladder hypersensitivity have been developed. The present application explores the role of corticotropin releasing factor receptors – type 2 (CRF2R) in this bladder hypersensitivity. Three Specific Aims are proposed: Specific Aim #1: To quantitatively characterize, using molecular and neurochemical measures, CRF2R expression and agonist peptide content in bladder primary afferent neurons (bPANs) & spinal cord of rats which had NBI & a second adult insult. Specific Aim #2: To quantitatively characterize effects of CRF2R agonists and antagonists on individual bPANs in rats which experienced NBI and a second adult insult. Specific Aim #3: To quantitatively characterize effects of CRF2R agonists and antagonists on spinal neuronal responses to UBD in rats which experienced NBI and a second adult insult. These studies will expand upon preliminary studies and will determine quantitatively the effects of the novel therapeutic agents, CRF2R-antagonists on primary afferent and spinal dorsal horn neuronal responses to UBD. Effects of pharmacological manipulations related to pain facilitation will be assessed in animals which experienced neonatal bladder inflammation and controls. The proposed studies in rodent model systems will give insight related to bladder pain and will explore novel therapeutics. An improved understanding of sensory processing related to IC and of urinary bladder sensory pathways and their modulation by secondary insults will result in an increased translation of basic science to therapeutics for bladder pain.

项目总结/摘要 源自膀胱的急性和慢性疼痛是常见的临床实体， 50%的女性在一生中的某个时候。为了了解膀胱超敏反应， 翻译的方式，这个正在进行的研究项目已经使用啮齿动物来定义基本的神经生理学 脊髓和脊髓上水平的膀胱感觉元素。使用膀胱扩张（UBD）诱发 反射和脊髓/脊髓上神经元反应作为实验终点， 膀胱超敏反应已经发展。本申请探索了促肾上腺皮质激素（corticotropin，ACTH）的作用。 释放因子受体2型（CRF 2 R）在这种膀胱超敏反应。三个具体目标是 提议的： 具体目标#1：使用分子和神经化学措施定量表征CRF 2 R 膀胱初级传入神经元（bPANs）和脊髓中的表达和激动剂肽含量 NBI和第二次成年损伤的大鼠。 具体目标#2：定量表征CRF 2 R激动剂和拮抗剂对个体 在经历NBI和第二次成年损伤的大鼠中的bPAN。 具体目标#3：定量表征CRF 2 R激动剂和拮抗剂对脊髓损伤的作用。 在经历NBI和第二次成人损伤的大鼠中，神经元对UBD的反应。 这些研究将在初步研究的基础上加以扩展，并将定量地确定小说的影响。 治疗剂、CRF 2 R拮抗剂对初级传入和脊髓背角神经元对 欠开发。将在动物中评估与疼痛促进相关的药理学操作的作用， 经历了新生儿膀胱炎症和对照。 在啮齿动物模型系统中进行的拟议研究将提供与膀胱疼痛相关的见解，并将探索 新疗法。提高对IC和膀胱感觉加工的认识 感觉通路及其通过二次损伤的调节将导致基本的 从科学到治疗膀胱疼痛