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（由申请人提供）：膀胱过度活动症 (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/BPS 对生活质量具有毁灭性的心理和社会影响，但治疗方法仍可。由于这些疾病在临床上具有挑战性，骶神经调节是 FDA 批准的治疗 OAB 的方法，目前仅在药物治疗失败后才提供给 OAB 患者。许多临床试验已证明骶神经调节可有效治疗 IC/BPS，目前已被 AUA 指南列为 IC/BPS 建议治疗方案之一。此外，临床研究表明阴部神经调节优于骶神经调节。它成功地治疗了骶神经调节失败的 OAB 或 IC/BPS 患者。此外，最近的多中心临床试验表明，胫骨神经调节对于治疗 OAB 是有效的。尽管神经调节是治疗 OAB 或 IC/BPS 的有效方法，但神经调节（骶骨、阴部或胫骨）的机制仍然未知。更令人惊讶的是，旨在揭示神经调节作用机制的基础科学研究非常有限。在这个项目中，我们建议通过回答以下问题来确定神经调节的中心作用位点：1.神经调节作用于脊髓还是大脑？2.它作用于上行还是大脑？由膀胱 A 激活的脊髓球脊髓排尿反射通路的降肢- 纤维传入或由有害 C 纤维膀胱传入激活的脊髓排尿反射通路？ 3. 哪些神经递质参与神经调节？ 4. 不同的神经调节方法如何与膀胱伤害感受/过度活动相关？骶骨、阴部或胫骨）将被研究和比较，以确定不同神经调节疗法的作用部位肯定会指导有利的。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。有关神经调节的作用位点和神经递质机制的信息也可用于开发治疗 OAB 或 IC/BPS 的新药物。 BPS。我们的研究将使数百万患有 OAB 或 IC/BPS 的美国人受益。