A developing view of the origins of urgency: the importance of animal models.

Although caution should be used when applying animal data to human physiology, if care is taken to differentiate between general principles and complications of detail, particular to the species being examined, then experimentation on animal models can reveal basic phenomena in the bladder that offer clues to the origin of urgency. Recent data from the whole isolated bladder of guinea pigs showed unexpected complexities in autonomous activity during the filling phase of the micturition cycle: small, transient increases in intravesical pressure were associated with propagating waves of contractile activity and localized stretches of bladder wall. This complex, coordinated activity suggests that there are mechanisms within the bladder wall devoted specifically to generating phasic activity. Thus, there appear to be two systems controlling detrusor contractions: one associated with overall contractions similar to the micturition contraction and the other generating phasic activity. The mechanisms generating the phasic activity appear to be the point of complex integration of both excitatory and inhibitory inputs. There is evidence that local activity in the bladder wall generates afferent discharge, which probably contributes to bladder sensations. Animal data suggest a novel motor/sensory system incorporating contractile (motor) events, which cause stretches resulting in activation of afferent nerves (sensory). The motor element of this system appears to be controlled in a highly complex fashion such that the amplitude and frequency of the motor activity can be modulated by a variety of inputs. This raises the possibility that the sensitivity of the system informing the central nervous system, and thus awareness of the bladder's state during the micturition cycle, can be manipulated, possibly via novel drugs targeted at areas involved in overactive bladder, including urgency incontinence.