Effect of botulinum toxin on detrusor overactivity induced by intravesical adenosine triphosphate and capsaicin in a rat model

Abstract

Objectives To assess the effects of intravesical injection of botulinum toxin type A (BTX) on a model of detrusor overactivity induced by intravesical infusions of adenosine triphosphate (ATP) and capsaicin. BTX has recently been used clinically to treat overactive bladder syndromes without a precise knowledge of the mechanism of action. Methods Twelve Sprague-Dawley rats underwent BTX injections. Six received 1.0 U and 6 received 0.5 U. BTX injections were done at bladder tube placement. Ten rats received saline injections as controls. After 48 hours of recovery, all 22 animals underwent awake, conscious cystometrography (CMG), performed using both saline and ATP (20 mM) intravesical infusion at 0.074 mL/min. In another 4 rats, capsaicin (100 μM) was infused intravesically before and after the BTX injections. The CMG parameters calculated included bladder contraction pressures and contraction frequencies (contractions per minute or Herz). Results Intravesical saline CMG produced a contraction frequency of 0.78 ± 0.10 Hz. Intravesical ATP doubled this voiding frequency to 1.45 ± 0.18 Hz ( P = 0.003). BTX treatment at 1.0 U reduced the frequency to 0.91 ± 0.13 Hz ( P = 0.02). BTX injection significantly decreased the bladder contraction pressure during saline and ATP CMG. However, 0.5 U BTX did not decrease ATP-induced overactivity; therefore, in the capsaicin experiments, 1.0 U BTX was used. Although BTX tended to reverse detrusor overactivity secondary to intravesical capsaicin, this difference was not statistically significant. Conclusions Intravesical infusion of either ATP or capsaicin can induce detrusor overactivity. BTX was more effective in blocking the effect of ATP than of capsaicin, although BTX injection did show a trend in reducing the contraction frequencies and amplitudes induced by capsaicin. The clinical utility of using BTX to treat overactive bladder syndromes and bladder hypersensory states, especially those that may be caused by an augmentation of the purinergic pathway, should be studied further.