Neurophysiology and therapeutic receptor targets for stress urinary incontinence

Abstract 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.