The neuro-urological connection

Urine storage and micturition are tightly controlled by the peripheral and central nervous systems. The parasympathetic pelvic nerves mediate signals for voiding, whereas the sympathetic hypogastric and the somatic pudendal nerves mediate signals for urine storage. Glutamate is a key transmitter of the descending neuronal pathways during the storage phase of the micturition cycle. Its effects on the activity of the hypogastric and pudendal nerves are modulated by serotonin and/or noradrenaline. Duloxetine inhibits the neuronal uptake of serotonin and noradrenaline and thereby enhances their effects in the central nervous system including the spinal nuclei responsible for urine storage. Thus, in a bladder irritation model in anaesthetised cats duloxetine dose-dependently restored bladder capacity and enhanced activity of the external urethral sphincter/rhabdosphincter. Such effects should prove beneficial in the treatment of patients with stress urinary incontinence. (C) 2004 Elsevier B.V. All rights reserved