Department of Biomedical Engineering, Florida International University, Miami, FL, USA.
Department of Biomedical Engineering, Duke University, Durham, NC, USA.
J Physiol. 2017 Aug 15;595(16):5687-5698. doi: 10.1113/JP274191. Epub 2017 Jul 7.
The lower urinary tract is regulated by reflexes responsible for maintaining continence and producing efficient voiding. It is unclear how sensory information from the bladder and urethra engages differential, state-dependent reflexes to either maintain continence or promote voiding. Using a new in vivo experimental approach, we quantified how sensory information from the bladder and urethra are integrated to switch reflex responses to urethral sensory feedback from maintaining continence to producing voiding. The results demonstrate how sensory information regulates state-dependent reflexes in the lower urinary tract and contribute to our understanding of the pathophysiology of urinary retention and incontinence where sensory feedback may engage these reflexes inappropriately.
Lower urinary tract reflexes are mediated by peripheral afferents from the bladder (primarily in the pelvic nerve) and the urethra (in the pudendal and pelvic nerves) to maintain continence or initiate micturition. If fluid enters the urethra at low bladder volumes, reflexes relax the bladder and evoke external urethral sphincter (EUS) contraction (guarding reflex) to maintain continence. Conversely, urethral flow at high bladder volumes, excites the bladder (micturition reflex) and relaxes the EUS (augmenting reflex). We conducted measurements in a urethane-anaesthetized in vivo rat preparation to characterize systematically the reflexes evoked by fluid flow through the urethra. We used a novel preparation to manipulate sensory feedback from the bladder and urethra independently by controlling bladder volume and urethral flow. We found a distinct bladder volume threshold (74% of bladder capacity) above which flow-evoked bladder contractions were 252% larger and evoked phasic EUS activation 2.6 times as often as responses below threshold, clearly demonstrating a discrete transition between continence (guarding) and micturition (augmenting) reflexes. Below this threshold urethral flow evoked tonic EUS activity, indicative of the guarding reflex, that was proportional to the urethral flow rate. These results demonstrate the complementary roles of sensory feedback from the bladder and urethra in regulating reflexes in the lower urinary tract that depend on the state of the bladder. Understanding the neural control of functional reflexes and how they are mediated by sensory information in the bladder and urethra will open new opportunities, especially in neuromodulation, to treat pathologies of the lower urinary tract.
下尿路受负责维持控尿和有效排尿的反射调节。目前尚不清楚膀胱和尿道的感觉信息如何通过差异的、状态依赖的反射来维持控尿或促进排尿。采用新的体内实验方法,我们量化了膀胱和尿道的感觉信息如何整合,从而将尿道感觉反馈的反射反应从维持控尿切换为产生排尿。结果表明了感觉信息如何调节下尿路的状态依赖反射,并有助于我们理解尿潴留和尿失禁的病理生理学,其中感觉反馈可能不恰当地激活这些反射。
下尿路反射是由来自膀胱(主要来自盆神经)和尿道(来自阴部和盆神经)的外周传入纤维介导的,以维持控尿或启动排尿。如果在膀胱容量较低时尿液进入尿道,反射会放松膀胱并引起外尿道括约肌(EUS)收缩(保护反射)以维持控尿。相反,在膀胱容量较高时尿道中的流动会兴奋膀胱(排尿反射)并放松 EUS(增强反射)。我们在麻醉的体内大鼠实验中进行了测量,以系统地描述通过尿道流动诱发的反射。我们使用了一种新颖的准备方法,通过控制膀胱容量和尿道流动来独立地操纵来自膀胱和尿道的感觉反馈。我们发现,在一个明显的膀胱容量阈值(膀胱容量的 74%)以上,流动诱发的膀胱收缩幅度增加 252%,并且触发相位性 EUS 激活的频率增加 2.6 倍,这明显表明了保护反射和增强反射之间的离散转换。在这个阈值以下,尿道流动诱发了紧张性 EUS 活动,表明存在保护反射,并且该活动与尿道流动速率成正比。这些结果表明,来自膀胱和尿道的感觉反馈在调节依赖于膀胱状态的下尿路反射中起着互补的作用。了解下尿路功能反射的神经控制以及它们如何通过膀胱和尿道的感觉信息介导,将为治疗下尿路疾病开辟新的机会,特别是在神经调节方面。