Neurotransmitter Receptors Involved in Neuromodulation of Bladder Overactivity

描述(申请人提供)：膀胱过度活动症(OAB)被国际大陆协会定义为一种以急迫性尿失禁为特征的综合征，通常伴有尿频和夜尿。OAB的病理和病因目前仍不清楚。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。骶神经调节是FDA批准的治疗OAB的方法。目前，它只提供给OAB患者在药物治疗失败后使用。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OAB患者，这些患者的骶骨神经调节失败。此外，最近的多中心临床试验表明，胫神经调节对OAB的治疗也是有效的。尽管神经调节是治疗OAB的有效方法，但神经调节的潜在机制(骶骨、阴部或胫骨)仍然未知，使得神经调节成为一种神秘的治疗方法。更令人惊讶的是，旨在揭示神经调节潜在机制的基础科学研究的努力非常有限。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)？相信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的治疗效果是天真的(�ve)。识别参与不同神经调节治疗的神经递质/受体将解开有关膀胱神经调节的谜团，并提供基础科学证据。它还将提供新的药物干预措施，进一步提高神经调节疗法的疗效。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。我们的研究将极大地造福数百万患有OAB的美国人。

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.