Neurophysiology and therapeutic receptor targets for stress urinary incontinence
Neurophysiology and therapeutic receptor targets for stress urinary incontinence
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DOI：
10.1111/j.1442-2042.2012.02976.x
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发表时间：
2012-06
影响因子：
2.6
通讯作者：
N. Yoshimura;M. Miyazato
中科院分区：
文献类型：
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作者：
N. Yoshimura;M. Miyazato
压力性尿失禁是女性尿失禁最常见的类型。压力性尿失禁涉及响应于由诸如打喷嚏和咳嗽的活动引起的腹部压力而不自主地泄漏尿液。这种情况影响着全世界数百万妇女，造成身体不适以及社会困扰，甚至社会孤立。这种类型的尿失禁通常见于中年后的女性，它可能是由于骨盆底薄弱或尿道括约肌支撑不良（尿道运动过度）和/或尿道括约肌系统受损（内在括约肌缺陷）导致的尿道闭合机制受损所致。直到最近，压力性尿失禁一直被临床医生视为一个纯粹的解剖学问题，由于尿道过度活动，需要行为或手术治疗。然而，据报道，内在括约肌缺陷与压力性尿失禁的相关性比尿道过度活动更显著。广泛的基础和临床研究增强了我们对调节下尿路正常功能的复杂神经回路的理解，以及可能导致压力性尿失禁发展的病理生理机制，并导致压力性尿失禁药物治疗的潜在新策略的发展。治疗靶点包括脊髓中的肾上腺素能受体和肾上腺素能受体，以及尿道括约肌处的肾上腺素能受体，其可分别增强应激条件下的尿道反射活动和增加基线尿道压力。本文就近年来压力性尿失禁的研究进展作一综述，并对尿道反射的神经生理学机制、压力性尿失禁的病因及药物治疗的潜在靶点进行讨论。
Stress urinary incontinence is the most common type of urinary incontinence in women. Stress urinary incontinence involves involuntary leakage of urine in response to abdominal pressure caused by activities, such as sneezing and coughing. The condition affects millions of women worldwide, causing physical discomfort as well as social distress and even social isolation. This type of incontinence is often seen in women after middle age and it can be caused by impaired closure mechanisms of the urethra as a result of a weak pelvic floor or poorly supported urethral sphincter (urethral hypermobility) and/or a damaged urethral sphincter system (intrinsic sphincter deficiency). Until recently, stress urinary incontinence has been approached by clinicians as a purely anatomic problem as a result of urethral hypermobility requiring behavioral or surgical therapy. However, intrinsic sphincter deficiency has been reported to be more significantly associated with stress urinary incontinence than urethral hypermobility. Extensive basic and clinical research has enhanced our understanding of the complex neural circuitry regulating normal function of the lower urinary tract, as well as the pathophysiological mechanisms that might underlie the development of stress urinary incontinence and lead to the development of potential novel strategies for pharmacotherapy of stress urinary incontinence. Therapeutic targets include adrenergic and serotonergic receptors in the spinal cord, and adrenergic receptors at the urethral sphincter, which can enhance urethral reflex activity during stress conditions and increase baseline urethral pressure, respectively. This article therefore reviews the recent advances in stress urinary incontinence research and discusses the neurophysiology of urethral continence reflexes, the etiology of stress urinary incontinence and potential targets for pharmacotherapy of stress urinary incontinence.