113 DECREASE OF UROTHELIAL CELL APOPTOSIS SIGNAL MOLECULES IS ASSOCIATED WITH IMPROVEMENT OF CLINICAL SYMPTOMS AFTER SINGLE INTRAVESICAL BOTULINUM TOXIN A INJECTION FOR PATIENTS WITH INTERSTITIAL CYSTITIS

Abstract

INTRODUCTION AND OBJECTIVES: Interstitial cystitis/painful bladder syndrome (IC/PBS) is considered to result from long-standing inflammation of bladder. Currently, no one treatment provides longterm efficacy. Intravesical botulinum toxin A (BoNT-A) injection seems to have promising therapeutic effect on IC/PBS. Several studies indicated that p38 MAPK activation is implicated in inflammation, fibrosis and mediating apoptosis in different cell types in various species. We have found that apoptosis of urothelial cells in IC/PBS could be due to up-regulation of inflammatory signals, including p38 MAPK and TNF . This study aimed to investigate whether the changes of bladder inflammation and apoptotic signal transduction could be modulated by intravesical BoNT-A injection in IC/PBS. METHODS: Twenty three patients with IC/PBS were enrolled. All patients received intravesical 100U BoNT-A injection. The bladder specimens were obtained at baseline and 6 months after the first injection. The double stain, protein array analysis and western blotting were performed to analyze the alterations of tryptase (mast cell activity), Bax, and phospho-p38 . The intensities of proteins in the arrays and Western blots were quantified using Image J processing. Inflammatory molecule treated urothelial cells were analyzed by TUNEL staining and western blotting for level of molecules involved in apoptosis. RESULTS: Clinical results after BoNT-A injection revealed improvement of visual analog score, O’Leary-Sant symptom score, and global response assessment but not glomerulation and maximal bladder capacity in overall patients (Table). Phospho-p38 and TUNEL double staining indicated that inflammatory and apoptotic events were co-existed in IC/PBS bladders. Analysis of the western blot results revealed significant decrease of phospho-p38 and Bax expression after the first time BoNT-A injection. However, the change of tryptase did not reach statistical significance. CONCLUSIONS: Single BoNT-A injection provides clinical improvement and reduce apoptotic signal protein production but mast cell activity did not significantly reduce, suggesting repeat BoNT-A injection is necessary to achieve long-term effect. Table. The changes of clinical measures and western blot measures parameters Baseline 6 months after BoNT-A P values VAS 5.30 2.46 3.78 2.61 0.048