Central Sites of Action for Bladder Neuromodulation

膀胱神经调节的中心作用位点

• 批准号: 8433699
• 负责人: Changfeng Tai
• 金额: $ 22.88万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8433699
• 关键词: Acetic Acids; American; Animals; Attention; Axon; Basic Science; Bladder; Bladder Diseases; Bladder Dysfunction; Brain; Brain Diseases; Brain Injuries; Brain imaging; C Fiber; Clinical; Clinical Research; Clinical Trials; Decerebration procedure; Disease; Effectiveness; Electric Stimulation; Emotions; Etiology; Excision; Exhibits; FDA approved; Felis catus; Fiber; Frequencies; Functional Magnetic Resonance Imaging; Goals; Guidelines; Human; Interstitial Cystitis; Knowledge; Limb structure; Methods; Micturition Reflex; Modeling; Motor Activity; Nerve; Neurotransmitters; Nociception; Outcome; Overactive Bladder; Parkinson Disease; Pathology; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacotherapy; Procedures; Prosencephalon; Psychological Impact; Quality of life; Research; Role; Sensory; Site; Social Impacts; Spinal; Spinal Cord; Spinal cord injury; Spinal nerve root structure; Structure of tibial nerve; Symptoms; Synaptic Transmission; Therapeutic Effect; Urinary Retention; Work; afferent nerve; base; clinical efficacy; drug development; effective therapy; expectation; human subject; improved; irritation; mind control; neuronal excitability; neuroregulation; neurotransmitter release; public health relevance; therapy outcome; treatment planning; treatment strategy

DESCRIPTION (provided by applicant): Overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS) are diseases with unknown pathology and etiology. OAB and IC/BPS have devastating psychological and social impacts on quality of life, but treatments for these diseases are clinically challenging. Sacral neuromodulation is a FDA approved treatment for OAB. Currently it is only offered to OAB patients after pharmacotherapy has failed. Since its FDA approval for OAB, sacral neuromodulation has been shown to be effective in treating IC/BPS in many clinical trials and is currently listed in the AUA guideline o IC/BPS as one of the suggested treatment options. In addition clinical studies have showed that pudendal neuromodulation is superior to sacral neuromodulation. It successfully treated OAB or IC/BPS patients who have failed sacral neuromodulation. Furthermore, recent multicenter clinical trials have indicated that tibial neuromodulation is effective for treatment of OAB. Although neuromodulation is an effective treatment for OAB or IC/BPS, the mechanism underlying neuromodulation (sacral, pudendal, or tibial) is still unknown. More surprisingly there is very limited effort in basic science research aimed at revealing the mechanism of action underlying neuromdulation. In this project we propose to determine the central sites of action for neuromodulation by answering the following questions: 1. whether neuromodulation acts in the spinal cord or in the brain? 2. Whether it acts on the ascending or descending limbs of the spinobulbospinal micturition reflex pathway activated by bladder A¿-fiber afferents or on the spinal micturition reflex pathway activated by noxious C-fiber bladder afferents? 3. What neurotransmitters are involved in neuromodulation? 4. How brain sensory and motor activity associated with bladder nociception/overactivity is altered by neuromodulation? Different neuromodulation methods (sacral, pudendal, or tibial) will be investigated and compared to answer these questions. Identifying the sites of action for different neuromodulation therapies will surely guide clinicians and patients in selection of the optimal treatment strategies and thereby significantly improve the clinical outcomes in treating OAB or IC/BPS. Information about the sites of action and the neurotransmitter mechanisms underlying neuromodulation could also be useful in developing new drugs to treat OAB or IC/BPS. Our studies will significantly benefit millions of Americans suffering from OAB or IC/BPS.

描述（由适用提供）：过度活跃的膀胱（OAB）和间质性膀胱炎/膀胱疼痛综合征（IC/BPS）是病理学和病因未知的疾病。 OAB和IC/BP对生活质量具有毁灭性的心理和社会影响，但是这些疾病的治疗方法在临床上受到挑战。 s骨神经调节是FDA批准的OAB治疗方法。目前，仅在药物治疗失败后才提供OAB患者。自从FDA批准OAB以来，s骨神经调节已被证明在许多临床试验中有效治疗IC/BPS，目前在AUA指南O IC/BPS中列为建议的治疗方案之一。此外，临床研究表明，底端神经调节优于s骨神经调节。它成功治疗了s骨神经调节失败的OAB或IC/BPS患者。此外，最近的多中心临床试验表明，胫骨神经调节可有效治疗OAB。尽管神经调节是OAB或IC/BPS的有效治疗方法，但仍未知神经调节（s骨，pudendal或胫骨）的机制尚不清楚。令人惊讶的是，基础科学研究的努力非常有限，旨在揭示神经瘤的作用机理。 In this project we propose to Determine the central sites of action for neuromodulation by answering the following questions: 1. Whether it acts on the ascending or descending limbs of the spinobulbospinal micturition reflex pathway activated by bladder A¿ -Fiber afferents or on the spinal micturition reflex pathway activated by noxious C-fiber bladeder afferents? 3。哪些神经递质参与神经调节？ 4。神经调节如何改变与膀胱伤伤心/过度运动相关的脑感觉和运动活性？将研究不同的神经调节方法（s骨，pudendal或胫骨），并进行比较以回答这些问题。确定不同神经调节疗法的作用部位肯定会指导临床医生和患者选择最佳治疗策略，从而显着改善治疗OAB或IC/BPS的临床结果。有关作用部位和神经调节基础神经递质机制的信息也可能对开发用于治疗OAB或IC/BPS的新药物很有用。我们的研究将大大使数百万患有OAB或IC/BP的美国人受益。