Detrusor myocyte activity and afferent signaling

Abstract

Aims: 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). Methods: Literature review of myocyte activation, bladder afferent nerves, mediators in the bladder, and translational aspects of the findings. Results: 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. Conclusions: 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. Neurourol.

Mechanisms involved in the nitric oxide independent inhibitory neurotransmission to the pig urinary bladder neck

“…These spontaneous contractions are able to generate activity in afferent nerves, that may contribute to detrusor overactivity. 12,13 In the pig bladder neck, the nonselective COX inhibitor indomethacin consistently promoted the apparition of phasic contractile activity, which suggests the possibility of a basal release of relaxant prostanoids from smooth muscle. Moreover, indomethacin reduced the relaxations evoked by nerve stimulation thus suggesting the involvement of COX-derived prostanoids.…”

NS19504: A Novel BK Channel Activator with Relaxing Effect on Bladder Smooth Muscle Spontaneous Phasic Contractions

“…Spontaneous nonvoiding contractions are not only a hallmark sign of overactive bladder, but are also believed to contribute to its pathogenesis (Brading, 1997;Andersson, 2010). Therefore, a compound capable of inhibiting nonvoiding contractions without affecting normal voiding elicited by nerve-evoked contractions may be considered to have a desired profile as a candidate to treat bladder overactivity.…”

Urothelial Signaling

“…A focus of current LUT research has been afferent mechanisms and the processes of how afferent information is generated and conveyed to the CNS in the control of micturition (11,13,153). One of the pathways defined involves the bladder mucosa, but attention has been given mainly to the urothelium (38).…”