Intravesical administration of exogenous NGF in animals can facilitate afferent firing and produce bladder hyperactivity, which is blocked by anti-NGF.93,94 Overexpression of NGF in the bladder

smooth muscle in spontaneously hypertensive rats leads to hyperinnervation of the bladder, which results in hyperactive voiding behavior.95 Stretching of the urothelium might induce production of NGF in the bladder tissue and secretion into the urine. Elevated urinary NGF levels play an important role in mediating the sensation of urgency in OAB. Therefore, NGF production can serve as a biomarker for neuroplasticity the some common pathway involved in the pathogenesis of OAB. Prostaglandin E2 (PGE2) synthesized in bladder muscle and mucosa has a complex local action in selleck the bladder. PGE2 affects the normal micturition reflex and under pathophysiological conditions (e.g. mucosa injury and inflammatory mediators).96 Intravesical administration of PGE2 stimulates reflex micturition through activation of capsaicin sensitive afferent nerves and causes bladder overactivity www.selleckchem.com/products/ldk378.html in rats and in humans.97,98 A previous study has suggested the association of inflammation with OAB symptoms by the

significant elevation of NGF and PGE2 levels in the urine of OAB patients.99 Liu et al. showed that urine NGF levels were very low in normal controls, while patients with OAB had significantly higher urinary NGF levels.100 Furthermore, OAB wet patients had significantly higher urinary NGF levels than OAB dry patients. This study concluded that elevated urinary NGF levels play an important role in mediating the sensation of urgency in OAB. The possible reason for the difference of NGF levels between OAB dry and OAB wet is the higher percentage of DO in patients with OAB wet. Furthermore, urine NGF level was decreased in association with the reduction of urgency severity in OAB patients who responded to intravesical botulinum toxin A injection or oral antimuscarinic therapy,101,102 but not in non-responders. Vorinostat clinical trial These results support urinary NGF level as a potential biomarker for evaluating a therapeutic outcome for OAB. Tyagi et al. collected midstream urine specimens from eight

asymptomatic control subjects and 17 idiopathic OAB patients.103 The urine was analyzed by a multiplex panel screen for 12 chemokines, cytokines, growth factors, and soluble receptors using Luminex multiplex ELISA technology (xMAP® technology, Affymetrix, Inc. Santa Clara, CA, USA). This analysis revealed a significant elevation of seven key inflammatory proteins in the urine of OAB patients relative to controls. This reported urinary chemokines profile in OAB patients corroborates the inference of severe inflammation in such patients.103 In a study of 179 biopsies obtained from 79 patients, 123 (63.1%) from 51 NDO patients and 56 (26.9%) from 28 IDO patients, Apostolidis et al. revealed signs of chronic inflammation were found in 59.1% of baseline biopsies (65.