Effective antimuscarinic treatment of OAB might act mainly on the muscarinic receptors in sensory pathways and alter urinary NGF production, which in turn reduces

the urgency sensation during bladder filling. If urinary NGF can be demonstrated to reduce in OAB patients with symptomatic improvement after antimuscarinic treatment, urinary NGF level could therefore buy GS-1101 be used as an objective tool to assess the therapeutic outcome of antimuscarinic treatment. Urinary NGF levels were measured in 38 normal controls and 70 patients with OAB. Patients were treated with tolterodine 4 mg once daily (QD). Urinary NGF/Cr levels and urgency severity scale (USS) were compared at baseline, 1, 2 and 3 months after antimuscarinics and 1 month after discontinuing treatment.42 This study demonstrated that urinary NGF levels decreased in association with the reduction of urgency severity and increased when OAB symptoms recurred. However, after antimuscarinic treatment for 3 months,

the mean USS had not decreased to zero and urinary NGF levels also remained significantly higher than those of controls. Elevated urinary NGF level might imply the existence of a residual inflammation in the bladder or central nervous system. In a recent study of urinary NGF levels in patients with cerebrovascular accident (CVA), NGF/Cr levels were found significantly higher in CVA patients than in normal subjects.43 Urinary NGF/Cr levels correlated well with the severity

of neurological impairment. Patients with mild/moderate impairment and severe impairment GSK-3 inhibition had significantly greater urinary NGF levels than that of none/minimal impairment, suggesting that urinary NGF might be a result of neurologic lesion rather than a cause of bladder dysfunction in CVA. However, previous studies in patients with OAB and DO found that about 30% of patients with OAB symptoms do not have an elevated urinary NGF level.37 It is difficult to explain why some OAB patients do not have elevated urinary NGF levels. Stress-related events may result in increased plasma NGF levels and involvement of neuroendocrine functions.44 Patients with OAB may have until symptoms which wax and wane without definite treatment. It is possible that the sources of NGF production in OAB might be either local (bladder) or systemic (central nervous system). Thus urinary NGF levels can fluctuate due to the effects of different general conditions and stress-related environments. Several urological diseases, including bacterial cystitis, lower ureteral stone, and urothelial cell carcinoma, may develop storage symptoms mimicking OAB or interstitial cystitis/painful bladder syndrome (IC/PBS). It is essential to understand whether these disorders can also produce a high amount of urinary NGF and whether increased urinary NGF production isrelatedto the associated storage symptoms in these diseases45.