Intravesical botulinum toxin a administration produces analgesia against acetic acid induced bladder pain responses in rats

Purpose: There is evidence that botulinum toxin A (BTX-A) might have analgesic properties. However, the mechanisms by which BTX-A alters pain remain largely unexplored. In the bladder afferent nerve fibers contain calcitonin gene-related peptide (CGRP). In this study we investigated the effect of intravesical BTX-A administration on CGRP immunoreactivity and bladder hyperactivity in an acetic acid induced bladder pain model in rats. Materials and Methods: Experimental and control animals were catheterized and intravesically exposed to protamine sulfate (1 ml, 10 mg/ml), followed by BTX-A (1 ml, 25 U/ml) or saline, y respectively. Three or 7 days after intravesical therapy continuous cystometrograms were performed using urethane anesthesia by filling the bladder (0.08 ml per minute) with saline, followed by 0.3% acetic acid. Bladder immunohistochemistry was used to detect CGRP. Results: The intercontraction interval (ICI) was decreased after acetic acid instillation (50.2% and 65.0%) in the control group at days 3 and 7, respectively. However, rats that received BTX-A showed a significantly decreased response (28.6% ICI decrease) to acetic acid instillation at day 7. This effect was not observed at day 3 (62.2% ICI decrease). Increased CGRP immunoreactivity was detected in the BTX treated group at day 7, which was not detected at day 3. Conclusions: Intravesical BTX administration blocked acetic acid induced bladder pain responses and inhibited CGRP release from afferent nerve terminals. These results support the clinical application of BTX-A for the treatment of interstitial cystitis and other types of visceral pain.