Mucosal signaling in the bladder

The bladder mucosa is comprised of the multilayered urothelium, lamina propria (LP), microvasculature, and smooth muscle fibers (muscularis mucosae). The muscularis mucosae is not always present in the mucosa, and its presence is related to the thickness of the LP. Since there are no mucus secreting cells, “mucosa” is an imprecise term. Nerve fibers are present in the LP of the mucosa. Efferent nerves mediate mucosal contractions which can be elicited by electrical field stimulation (EFS) and various agonists. The source of mucosal contractility is unknown, but may arise from the muscularis mucosae or myofibroblasts. EFS also increases frequency of mucosal venule contractions. Thus, efferent neural activity has multiple effects on the mucosa. Afferent activity has been measured when the mucosa is stimulated by mechanical and stretch stimuli from the luminal side. Nerve fibers have been shown to penetrate into the urothelium, allowing urothelial cells to interact with nerves. Myofibroblasts are specialized cells within the LP that generate spontaneous electrical activity which then can modulate both afferent and efferent neural activities. Thus mucosal signaling is defined as interactions between bladder autonomic nerves with non-neuronal cells within the mucosa. Mucosal signaling is likely to be involved in clinical functional hypersensory bladder disorders (e.g. overactive bladder, urgency, urgency incontinence, bladder pain syndrome) in which mechanisms are poorly understood despite high prevalence of these conditions. Targeting aberrant mucosal signaling could represent a new approach in treating these disorders.