Neurotransmitter Receptors Involved in Neuromodulation of Bladder Overactivity

参与膀胱过度活动神经调节的神经递质受体

• 批准号: 9117512
• 负责人: Changfeng Tai
• 金额: $ 23.1万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9117512
• 关键词: Adult; Adverse effects; American; Applications Grants; Axon; Basic Science; Bladder; Brain; Chemicals; Clinical; Clinical Research; Clinical Trials; Complex; Etiology; FDA approved; Felis catus; Frequencies; Glycine Receptors; Health; International; Intervention; Left; Mediating; Metabotropic Glutamate Receptors; Micturition Reflex; Nerve; Neurotransmitter Receptor; Neurotransmitters; Nocturia; Opioid; Opioid Receptor; Overactive Bladder; Pathology; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacotherapy; Plant Roots; Play; Psychological Impact; Quality of life; Rattus; Reflex action; Research; Role; Social Impacts; Societies; Spinal Cord; Spinal nerve root structure; Structure of tibial nerve; Synapses; Syndrome; Therapeutic Effect; United States; Urge Incontinence; Work; base; drug development; effective therapy; human subject; improved; metabotropic glutamate receptor 2; metabotropic glutamate receptor 4; neuroregulation; neurotransmitter release; novel therapeutics; receptor; somatic afferent nerve; therapy outcome

DESCRIPTION (provided by applicant): Overactive bladder (OAB) is defined by the International Continence Society as a syndrome characterized by urgency with or without urge incontinence, usually with frequency and nocturia. The pathology and etiology of OAB currently remain unknown. OAB has devastating psychological and social impacts on quality of life, but treatments for OAB are clinically challenging. Sacral neuromodulation is a FDA approved treatment for OAB. Currently it is only offered to OAB patients after pharmacotherapy has failed. In addition, clinical studies have showed that pudendal neuromodulation is superior to sacral neuromodulation. It successfully treated OAB patients who have failed sacral neuromodulation. Furthermore, recent multicenter clinical trials have indicated that tibial neuromodulation is also effective for OAB treatment. Although neuromodulation is an effective treatment for OAB, the mechanisms underlying neuromodulation (sacral, pudendal, or tibial) are still unknown leaving neuromodulation as a mysterious therapy. More surprisingly there is very limited effort in basic science research aimed at revealing the possible mechanisms underlying neuromdulation. In this project we propose to elucidate the mechanisms underlying neuromodulation of bladder overactivity by answering the following question: what neurotransmitter receptors are involved in the different types of neuromodulation (sacral, pudendal, or tibial)? It would be na�ve to believe that the different neuromodulation therapies utilize the same neurotransmitter mechanisms to achieve the therapeutic effects on OAB conditions. Identifying the neurotransmitters/receptors involved in different neuromodulation therapies will remove the mysteries around bladder neuromodulation and provide basic science evidences. It will also provide new pharmacological interventions to further improve the efficacy of neuromodulation therapy. Information about the neurotransmitter mechanisms underlying neuromodulation could also be useful in developing new drugs to treat OAB. Our studies will significantly benefit millions of Americans suffering from OAB.

描述（由申请人提供）：膀胱过动症（OAB）被国际尿失禁协会定义为一种以急迫性伴或不伴急迫性尿失禁为特征的综合征，通常伴有尿频和夜尿。OAB的病理和病因目前尚不清楚。OAB对生活质量有毁灭性的心理和社会影响，但OAB的治疗在临床上具有挑战性。骶骨神经调节是FDA批准的治疗OAB的方法。目前，它只提供给药物治疗失败的OAB患者。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患者。此外，最近的多中心临床试验表明，胫骨神经调节对OAB治疗也是有效的。尽管神经调节是OAB的有效治疗方法，但神经调节（骶骨、阴部或胫骨）的机制仍然未知，使神经调节成为一种神秘的治疗方法。更令人惊讶的是，在揭示神经调节可能机制的基础科学研究中，所做的努力非常有限。在这个项目中，我们建议通过回答以下问题来阐明膀胱过度活动的神经调节机制：哪些神经递质受体参与不同类型的神经调节（骶骨、阴部或胫骨）？如果认为不同的神经调节疗法利用相同的神经递质机制来达到对OAB的治疗效果，那就太天真了。识别参与不同神经调节疗法的神经递质/受体将揭开膀胱神经调节的神秘面纱，并提供基础科学证据。它也将为进一步提高神经调节治疗的疗效提供新的药理干预措施。有关神经调节的神经递质机制的信息也可能有助于开发治疗OAB的新药。我们的研究将极大地造福数百万患有OAB的美国人。