Elsevier

Urology

Volume 65, Issue 3, March 2005, Pages 622-626
Urology

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

https://doi.org/10.1016/j.urology.2004.10.057Get rights and content

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.

Section snippets

Bladder tube placement

The rats were anesthetized with halothane general anesthesia. The bladders were exposed through a midline incision. A Clay-Adams PE-50 (polyethylene) tube (1 mm outer diameter) was placed through a small incision in the dome of the bladder. The bladder was closed in a purse-string manner. The PE-50 tube was then tunneled under the subcutaneous tissue and exited through the interscapular space. A Covance infusion harness was used to secure the tube. The University of Maryland IUCAC approved all

CMG tracings

Figure 1 depicts representative CMG tracings from the experiments. Figure 1A is of a saline CMG. Figure 1B shows detrusor overactivity in response to intravesical infusion of 20 mM ATP. Figure 1C shows the effect of intravesical 100 μM capsaicin. Representative CMG tracings from animals treated to 1.0 U BTX and then infused with ATP and capsaicin are shown in Figure 1D and Figure 1E, respectively.

Effect of BTX on detrusor overactivity induced by ATP

ATP infusion into the rat bladder significantly increased the frequency of bladder contractions

Comment

The symptom complex of OAB represents both a diagnostic and a treatment dilemma for the urologist. First, it is a diagnosis of exclusion, because no pathognomonic criterion is available to confirm an OAB. Because of this, treatment is empiric and directed at stopping the presumed unwanted bladder contractions. Ideally, a drug should also stop or diminish the sense of bladder urgency. It is along these lines that antimuscarinics, such as oxybutynin and tolterodine, have been developed to treat

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This study was supported by a minigrant from the National Kidney Foundation of Maryland.

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