Neurotransmitter Receptors Involved in Neuromodulation of Bladder Overactivity

描述（由申请人提供）：膀胱过度活动症（OAB）由国际尿失禁协会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，通常伴有尿频和尿失禁。OAB的病理学和病因学目前仍不清楚。OAB对生活质量具有破坏性的心理和社会影响，但OAB的治疗在临床上具有挑战性。骶神经调节是FDA批准的OAB治疗方法。目前，它只提供给药物治疗失败后的OAB患者。此外，临床研究表明阴部神经调节上级骶神经调节。它成功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，胫神经调节对OAB治疗也有效。虽然神经调节是OAB的有效治疗方法，但神经调节（骶骨、阴部或胫骨）的潜在机制仍不清楚，使神经调节成为一种神秘的治疗方法。更令人惊讶的是，在基础科学研究中，旨在揭示神经调节的可能机制的努力非常有限。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：什么样的神经递质受体参与不同类型的神经调节（骶骨，阴部，或胫骨）？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病症的治疗效果是天真的。明确不同神经调节疗法中的神经递质/受体，将有助于揭开膀胱神经调节的神秘面纱，为膀胱神经调节提供基础科学依据。它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疗效。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。我们的研究将使数百万患有OAB的美国人受益匪浅。

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.