Abstract
Overactive bladder (OAB) syndrome is associated with increased spontaneous contractions of the bladder wall, potentially mediated by the release of chemical agents from the urothelium. Reduction of these spontaneous contractions offers a means to alleviate the symptoms of OAB. I tested two novel approaches using pig bladder in vitro or ex vivo preparations; bladder wall heating or injection of inert bulking agents. In vitro, intact (mucosa + detrusor muscle) preparations were heated to 42, 46, or 50oC by a heating coil. Preparations of only detrusor muscle or mucosa were heated by changing superfusate temperature. Experiments were done to examine the role of heat-sensitive TRPV1 channels during heating by using TRPV1 antagonists. The effect of heating on urothelium ATP release was also measured. Possible changes to tissue structure were histologically assessed with haematoxylin & eosin or van Gieson staining. Inert bulking agents (Tyrode’s, polyethylene glycol or coaptite) were injected into the sub-mucosal space and their effect on spontaneous contractions also measured. Ex vivo experiments with perfused pig bladders recorded spontaneous pressure variations when perfusate temperature was increased to 42°C. Spontaneous contractions in intact preparations were reversibly reduced when heated to 42, 46, or 50oC; TRPV1 antagonists had no effect. Heating to 42oC did not affect mucosa or detrusor-only preparations, but at 50°C contractions were abolished. Similar effects were seen in ex vivo experiments when heated to 42°C. No changes to tissue integrity were observed at 42 or 46°C. At all temperatures urothelial ATP release was increased. Spontaneous contractions were reduced by all bulking agents, coaptite was the most effective. These novel findings suggest possible clinical approaches to treat the symptoms of OAB by reducing spontaneous contractions.