18 In p38 MAPK activation patients with painful bladder syndrome/interstitial cystitis (PBS/IC), neurotrophins, including NGF, neurotrophin-3, and glial cell line-derived neurotrophic factor, have been detected in the urine.19 Increased expression of NGF is also present in bladder biopsies from women with PBS/IC.20 Thus, target organ-neural interactions mediated by an increase of neurotrophins in the bladder and increased transport of neurotrophins to the neuronal cell bodies Inhibitors,research,lifescience,medical in afferent pathways may contribute to the emergence of bladder pain in PBS/IC.8 Patients with PBS/IC who responded to intravesical botulinum toxin injection have been found

to have reduced bladder tissue NGF expression (Figure 2).21 Figure 2 Increased nerve growth factor (NGF)

expression in the apical cells of urothelium, suburothelium, and nerves were noted in a patient with painful bladder syndrome/interstitial cystitis Inhibitors,research,lifescience,medical (red arrows, A) and decreased in response to intravesical botulinum … In the urinary tract, NGF is produced by urothelium and smooth muscle.18 Clinical and experimental data indicate a direct link between increased levels of NGF in bladder tissue and urine and painful inflammatory conditions in the lower urinary tract, such as bladder outlet obstruction (BOO), OAB, PBS/IC, and Inhibitors,research,lifescience,medical chronic prostatitis.18–20 Increased levels of NGF have also been reported in the bladder tissue and urine of patients with sensory urgency and DO.22,23

Studies on NGF in OAB or DO usually measure the bladder tissue level. A recent study measuring NGF concentration using enzyme-linked immunosorbent assay (ELISA) in superficial Inhibitors,research,lifescience,medical bladder biopsies from 12 women with DO and 15 without urodynamic DO did not show a significant correlation with tissue NGF level.24 It is impossible to standardize the quantity of epithelium; suburothelium and muscle with a bladder biopsy and this study confirm our experience that urine NGF measurement is a simple, Inhibitors,research,lifescience,medical safe, and more accurate assay, and one however that can be standardized. Evidence has shown that visceral epithelia are a major source of NGF production and that NGF may regulate the function of adult visceral sensory and motor neurons.25 The level of NGF in urine could increase bladder sensation or cause DO through some undetermined pathway.11 If the urinary NGF level differs among normal controls and patients with increased bladder sensation, OAB dry, or OAB wet, then urinary NGF level could be a biomarker for diagnosing OAB or assessing therapeutic outcome. Kim and colleagues26 found that urinary NGF levels increase in men and women with OAB syndrome. Yokoyama and associates27 evaluated urine NGF in 51 OAB patients that included men and women with DO, OAB without DO, BOO, and neurogenic DO.