Therapeutic new targets for stress urinary incontinence in the central nervous system

Abstract

Stress urinary incontinence (SUI) is a common and bothersome problem among middle-aged women. However, there are few useful drugs for SUI. Urethral hypermobility and intrinsic sphincter deficiency are two main causes of SUI. Various animal models of SUI, such as vaginal distention, pudendal nerve injury, or ovariectomy, have been developed to study the pathophysiology of SUI. In addition, we have previously reported that cerebral infarction rats also induce SUI. Leak point pressure measurements are the most commonly used methods to evaluate the urethral dysfunction in SUI animal models. Originally, we have developed microtransducer-tipped catheter measurements of urethral activity during sneezing. Previous or our basic research has clarified potential strategies for pharmacotherapy of SUI in the central nervous system. Therapeutic targets include adrenergic and serotonergic (5-HT) receptors in the spinal cord, which stimulate pudendal nerve innervating the external urethral sphincter and/or sympathetic nerve innervating urethral smooth muscle. Activation of α1-adrenoceptors, 5-HT2C, or 5-HT7 receptors enhances the reflex at the spinal cord level whereas pre- or postsynaptic α2-adrenoceptors and/or 5-HT1A receptors inhibit the reflex. We have recently reported that stimulation of the spinal μ-opioid receptors by tramadol also enhances the reflex. Thus, we review the recent advances in basic SUI research and potential targets for pharmacotherapy of SUI in the central nervous system.