Developments in our understanding of detrusor instability.

It is important to recognize that our understanding of detrusor instability is far from complete. Although the significance of some of the abnormalities reported is unclear, it is likely that several factors will eventually be found to contribute to the overall clinical picture. Nevertheless, there is increasing evidence that the development of post-junctional supersensitivity of the detrusor muscle is implicated in each of the clinical subgroups of instability. Partial denervation of the detrusor appears to be the mechanism responsible for this in obstructive detrusor instability, but other abnormalities causing a chronic decrease in the excitatory motor innervation to the detrusor (e.g. decentralization, pre-synaptic inhibition) could produce similar effects and may therefore be involved. This evidence of a specific abnormality at the cellular level offers scope for therapy for detrusor instability with a new range of drugs, using agents that hyperpolarize the detrusor muscle membrane or modify calcium activation. However, bladder specificity remains a fundamental problem in the development of effective therapeutic agents for detrusor instability and poses the great challenge for the future.