Detrusor myocyte activity and afferent signaling

Abstract

To discuss (1) mechanisms involved in the generation and control of myocyte contractions and consequent afferent nerve activity and (2) these mechanisms as targets for drugs aimed for treatment of overactive bladder (OAB) symptoms and detrusor overactivity (DO). Literature review of myocyte activation, bladder afferent nerves, mediators in the bladder, and translational aspects of the findings. During bladder filling, there is normally no parasympathetic outflow from the spinal cord. Despite this, the bladder develops tone during filling and also exhibits non-synchronized local contractions and relaxations that are caused by a basal myogenic mechanical activity that may be reinforced by release of, for example, acetylcholine from non-neuronal and/or neuronal sources or local mediators, such as prostaglandins and endothelins. It is suggested that these spontaneous contractions are able to generate activity in afferent nerves ("afferent noise") that may contribute to DO and OAB. Spontaneous bladder myocyte contractions and factors that are able to modulate them, as well as the consequent afferent nerve activity, may be targets for drugs meant for treatment of OAB/DO.