Impact of overactive bladder on the brain: central sequelae of a visceral pathology

Neural circuits that allow for reciprocal communication between the brain and viscera are critical for coordinating behavior with visceral activity. At the same time, these circuits are positioned to convey signals from pathologic events occurring in viscera to the brain, thereby providing a structural basis for comorbid central and peripheral symptoms. In the pons, Barrington's nucleus and the norepinephrine (NE) nucleus, locus coeruleus (LC), are integral to a circuit that links the pelvic viscera with the forebrain and coordinates pelvic visceral activity with arousal and behavior. Here, we demonstrate that a prevalent bladder dysfunction, produced by partial obstruction in rat, has an enduring disruptive impact on cortical activity through this circuit. Within 2 weeks of partial bladder obstruction, the activity of LC neurons was tonically elevated. LC hyperactivity was associated with cortical electroencephalographic activation that was characterized by decreased low-frequency (1-3 Hz) activity and prominent theta oscillations (6-8 Hz) that persisted for 4 weeks. Selective lesion of the LC-NE system significantly attenuated the cortical effects. The findings underscore the potential for significant neurobehavioral consequences of bladder disorders, including hyperarousal, sleep disturbances, and disruption of sensorimotor integration, as a result of central noradrenergic hyperactivity. The results further imply that pharmacological manipulation of central NE function may alleviate central sequelae of these visceral disorders.