Neural control of the bladder

Abstract

Normal bladder function includes a storage phase and a voiding or micturition phase, which are controlled by neural circuits integrated at the level of the forebrain, brainstem, and spinal cord. Urine storage depends on lumbosacral spinal reflexes, whereas normal micturition involves a spino-bubo-spinal reflex mediated by the pontine micturition center (PMC). Behavioral and emotional influences affect the micturition reflex via integration of inputs from the frontal lobe and bladder afferents at the level of the periaqueductal gray (PAG). Experimental studies in animals and functional neuroimaging studies in humans have provided abundant information into the normal mechanisms of micturition, including the role of the bladder urothelium, plasticity of the spinal micturition reflexes, and behavioral control of micturition by cortical networks. This information has provided new insight into the pathophysiology of neurogenic bladder, including detrusor overactivity, in spinal cord and other neurologic disorders. There are recent excellent reviews by investigators who have contributed to the current understanding of bladder control mechanisms.1,–,5 Only few salient concepts will be emphasized here. ### Urothelium and mechanosensory transduction. The urothelium is the epithelial lining of the lower urinary tract and includes a superficial layer composed of large hexagonal cells, called “umbrella cells”; these cells are interconnected by tight junctions and covered by crystalline proteins called uroplakins.2,6 The urothelium has a major role in mechanosensory transduction via reciprocal interactions with afferent and efferent nerves (figure 1). During bladder filling, the umbrella cells release several chemical signals, including acetylcholine (ACh), nitric oxide (NO), and adenosine triphosphate (ATP), which alter the excitability of afferent fibers. For example, ATP, acting via P2X and P2Y receptors, excites C-fiber afferents by reducing threshold of activation of transient receptor potential vanilloid type 1 (TRPV1) channels. ATP also acts as an autocrine signal between urothelial cells and as a paracrine signal …