Quantitative Study of Urinary Bladder Sensory Processing

膀胱感觉处理的定量研究

• 批准号: 6881447
• 负责人: TIMOTHY J NESS
• 金额: $ 24.43万
• 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 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6881447
• 关键词: analgesics; dorsal horn; electromyography; electrophysiology; experimental brain lesion; female; hypersensitivity; laboratory mouse; laboratory rat; microelectrodes; neural information processing; neurophysiology; nociceptors; opioid receptor; pain; reflex; sensory neuropathy; single cell analysis; spinal nerves; stimulant /agonist; stimulus /response; urinary bladder disorder; urinary tract motility /pressure; visceral afferent nerve

DESCRIPTION (provided by applicant): 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. Some conditions are easy to treat, but others, such as interstitial cystitis, are conditions of visceral hypersensitivity that have proven resistant to diagnosis and treatment. There are multiple proposed etiologies for visceral hypersensitivity conditions including mast cell functional abnormalities, immunologic abnormalities, urothelial abnormalities and primary neuropathic mechanisms but the common theme among them is an eventual sensitization/activation of sensory elements. Abnormalities in the periphery leads to central neurophysiological changes that become expressed as enhanced sensory (pain-urgency) and reflex responses (i.e. reduced bladder capacity) which may outlast "triggering" events within the bladder. This proposal defines the consequences of altered primary afferent function by examining the spinal sites of sensory processing which magnify and prolong the effects of peripheral processes. The hypothesis central to these studies is the following: Pathological urinary bladder pain occurs secondary to a 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 delineate mechanisms of this sensitization process, testable hypotheses are proposed: first, that sensitization occurs secondary to the selective activation of one of two spinal dorsal horn neuronal populations; second, that a driving force of this sensitization process is the activation of peripheral K-opioid receptor expressing primary afferents; and finally, it is proposed that spinal neurons which are selectively activated by visceral pain-producing manipulations have axonal projections located in the mid-dorsal spinal cord. To test the critical aspects of these hypotheses, neuronal and physiological responses to urinary bladder distension will be studied. Information gathered as part of these studies will allow for an improved definition of urinary bladder-related spinal nociceptive processing mechanisms and will suggest novel therapeutic interventions for urinary bladder pain which include the use of peripherally acting analgesics and modulation/interruption of selective pain pathways. To allow for methodological expansion, characterization of responses to urinary bladder distension in mice will also be examined.

描述（由申请人提供）：源自膀胱的急性和慢性疼痛是常见的临床实体，影响超过50%的女性在其生命中的某个时间。有些情况很容易治疗，但其他情况，如间质性膀胱炎，是内脏高敏感性的条件，已被证明耐诊断和治疗。内脏高敏感性疾病有多种病因，包括肥大细胞功能异常、免疫异常、尿路上皮异常和原发性神经病理机制，但它们之间的共同主题是感觉元件的最终致敏/激活。外周神经功能减退导致中枢神经生理学变化，表现为增强的感觉（疼痛-紧迫感）和反射反应（即膀胱容量减少），其持续时间可能超过膀胱内的“触发”事件。该建议通过检查放大和延长外周过程影响的感觉处理的脊髓部位来定义初级传入功能改变的后果。这些研究的核心假设如下： 病理性膀胱疼痛继发于由重复或连续的初级传入激活产生的脊髓致敏过程，其导致超敏状态，其中先前无害的刺激产生疼痛。 为了阐明这种致敏过程的机制，提出了可检验的假说：第一，致敏发生于两个脊髓背角神经元群中的一个的选择性激活，第二，这种致敏过程的驱动力是表达初级传入的外周K-阿片受体的激活，第三，这种致敏过程的驱动力是表达初级传入的外周K-阿片受体的激活。最后，有人提出，选择性激活的内脏疼痛产生的操作脊髓神经元有轴突投射位于中背侧脊髓。为了测试这些假设的关键方面，神经元和生理反应膀胱扩张将进行研究。作为这些研究的一部分收集的信息将允许膀胱相关的脊髓伤害性处理机制的改进定义，并将建议新的治疗干预膀胱疼痛，其中包括使用外周作用镇痛药和调制/选择性疼痛通路中断。为了允许方法学扩展，还将检查小鼠对膀胱扩张的反应的表征。