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

基本信息

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
项目类别：
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

项目摘要

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）：国际尿控协会将膀胱过度活动症（OAB）定义为一种以尿急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 的病理学和病因目前仍不清楚。心理和社会影响生活质量，但 OAB 的治疗在临床上具有挑战性，是 FDA 批准的 OAB 治疗方法，目前仅提供给药物治疗后的 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，尽管神经调节治疗失败，但胫骨神经调节也有效。虽然神经调节（骶骨、阴部或胫骨）是治疗 OAB 的有效方法，但其机制仍然未知，这使得神经调节成为一种神秘的疗法。旨在揭示神经调节潜在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实现对 OAB 病症的治疗效果，那就太天真了。参与不同神经调节治疗的神经递质/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，这还将提供新的药理学干预措施，以进一步提高神经调节治疗的功效。有关神经调节背后的神经递质机制的信息也可能有助于开发。我们的治疗 OAB 的新药物研究将使数百万患有 OAB 的美国人受益。