Neurotrophins in bladder function: what do we know and where do we go from here?

Neurotrophins (NTs) have attracted considerable attention in the urologic community. The reason for this resides in the recognition of their ability to induce plastic changes of the neuronal circuits that govern bladder function. In many pathologic states, urinary symptoms, including urgency and urinary frequency, reflect abnormal activity of bladder sensory afferents that results from neuroplastic changes. Accordingly, in pathologies associated with increased sensory input, such as the overactive bladder syndrome (OAB) or bladder pain syndrome/interstitial cystitis (BPS/IC), significant amounts of NTs have been found in the bladder wall.

Here, current knowledge about the importance of NTs in bladder function will be reviewed, with a focus on the most well-studied NTs, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF).

Both NTs are present in the bladder and regulate bladder sensory afferents and urothelial cells. Experimental models of bladder dysfunction show that upregulation of these NTs is strongly linked to bladder hyperactivity and, in some cases, pain. NT manipulation has been tested in animal models of bladder dysfunction, and recently, NGF downregulation, achieved by administration of a monoclonal antibody, has also been tested in patients with BPS/IC and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). NTs have also been found in high quantities in the urine of OAB and BPS/IC patients, raising the possibility of NTs serving as biomarkers.

Available data show that our knowledge of NTs has greatly increased in recent years and that some results may have future clinical application.