QUANTITATIVE STUDY OF URINARY BLADDER SENSORY PROCESSING

膀胱感觉处理的定量研究

• 批准号: 2713436
• 负责人: TIMOTHY J NESS
• 金额: $ 10.67万
• 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 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2713436
• 关键词: NMDA receptors; female; hyperalgesia; interstitial cystitis; laboratory rat; neuroregulation; neurotransmitter antagonist; pain; sensory neuropathy; sensory receptors; visceral afferent nerve

Acute and chronic pains originating from the urinary bladder are common clinincal entities. Some conditions are easy to treat, but others such as interstitial cystitis have proved resistant to diagnosis and treatment. Interstitial cystitis can be described as a visceral neuropathic pain, a hypersensitivity state that is secondary to a site of irritation (a peripheral generator) located in the urinary bladder. It has been estimated to afflict 90,000-450,000 Americans, mainly women. Frustrated and at a loss for effective treatments, some patients have undergone surgical removal of their bladders, only to have continued pain. Attempts to understand and treat this disorder have examined the peripheral generator. This application proposes to extend our field of interest to the spinal sites of sensory processing which may magnify and prolong the effects of peripheral processes. The hypothesis central to the proposed studies is the following: Urinary bladder pain occurs secondary to a N-methyl-D-aspartate glutamate receptor-mediated, spinal, sensitization process produced by repeated or continuous primary afferent activation which leads to a hypersensitivity state in which previously innocuous stimuli produce pain. To test the critical elements of this hypothesis, the elements of spinal visceral nociceptive processing will be defined in halothane- anesthetized, female rats utilizing methodology developed in studies of gut sensation. Studies of primary afferent nerve pathways and physiologic responses in the rat will generate necessary parallel information that will allow for proper interpretation of spinal neuronal data. Neuronal and physiologic responses to urinary bladder distension will also be examined in rats receiving manipulations demonstrated to produce hypersensitivity (inflammation) or prevent hypersensitivity (N- methyl-D-aspartate receptor antagonists) in other model systems. The quantitative studies or urinary bladder sensation proposed in this grant application will test a hypothetical model of visceral nociception and will assess whether a novel group of analgesics, the N-methyl-D-aspartate glutamate receptor antagonists, may have efficacy in the treatment of visceral hypersensitivity states such as interstitial cystitis.

急性和慢性疼痛起源于膀胱， 常见的临床实体 有些情况很容易治疗，但 其他如间质性膀胱炎已被证明对诊断有抵抗力 和治疗。 间质性膀胱炎可以被描述为一种内脏性膀胱炎。 神经性疼痛，一种继发于一个部位的超敏状态， 刺激（外周发生器）位于膀胱。 据估计，有90，000 - 450，000美国人受到影响，主要是 妇女 一些人感到沮丧，对有效的治疗方法不知所措， 患者接受了膀胱切除手术，结果却发现 持续的疼痛。 试图理解和对待这一点 检查了外围发电机 本申请 建议将我们感兴趣的领域扩展到脊柱部位， 感官处理，可以放大和延长的影响， 外围进程 提出的假设的核心是 研究如下： 膀胱疼痛继发于N-甲基-D-天冬氨酸 谷氨酸受体介导的脊髓致敏过程 通过重复或连续的初级传入激活， 到一种过敏状态，在这种状态下，以前无害的刺激 产生疼痛。 为了检验这一假设的关键要素， 脊髓内脏伤害性处理将在氟烷中定义， 麻醉的雌性大鼠，采用 对内脏感觉的研究 初级传入神经的研究 在大鼠中的通路和生理反应将产生 必要的平行信息，将允许适当的 脊髓神经元数据的解释。 神经和生理 对膀胱扩张的反应也将在 接受操作的大鼠被证明产生 过敏（炎症）或预防过敏（N- 甲基-D-天冬氨酸受体拮抗剂）。 膀胱感觉的定量研究 这项拨款申请将测试一个假设的模型， 并将评估是否有一组新的镇痛药， 所述N-甲基-D-天冬氨酸谷氨酸受体拮抗剂可 在治疗内脏高敏感状态方面有效 例如间质性膀胱炎。