Pathologic mechanism of the therapeutic effect of botulinum toxin A on interstitial cystitis and painful bladder syndrome

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder condition characterized by bladder pain, frequency and nocturia. There is no definite treatment providing a long-term cure for IC/PBS. Recent studies have demonstrated that intravesical botulinum toxin A (BoNT-A) has promising effects on IC/PBS. Repeated BoNT-A injections might provide long-term symptom relief and decrease glomerulations after cystoscopic hydrodistention. Our previous studies demonstrated bladder tissue nerve growth factor is elevated in IC/PBS bladders and decreased in responders to BoNT-A injection associated with decreased visual analog pain scores. Another study revealed that increased urothelial cell apoptosis, decreased cell proliferation, increased mast cell activation, and impaired expression of junction protein E-cadherin were significant in IC/PBS bladders. Further study of apoptotic markers and inflammatory protein expression also revealed that apoptotic signaling molecules, including Bad, Bax, and caspase 3, were increased in the bladder tissues of patients with IC/PBS. The apoptosis and growth arrest of bladder tissues of IC/PBS patients could be due to upregulation of inflammatory signals, including p38 mitogen-activated protein kinase and tumor necrosis factor alpha. We reviewed the possible pathologic mechanisms of the therapeutic effects of intravesical BoNT-A injection and presented the results of our pilot studies of BoNT-A injections for IC/PBS.