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


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, 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.
Chuang
Yao-Chi
YC
Department of Urology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Yoshimura
Naoki
N
Huang
Chao-Cheng
CC
Chiang
Po-Hui
PH
Chancellor
Michael B
MB
D019342:Acetic Acid / Q000633:toxicity*; D000283:Administration, Intravesical; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism; D003556:Cystitis / Q000139:chemically induced / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D009122:Muscle Hypertonia / Q000139:chemically induced; D009619:Nociceptors / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects*; D011479:Protamines / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation / Q000473:pathology; D014563:Urodynamics
D011479:Protamines; D019274:Botulinum Toxins, Type A; D015740:Calcitonin Gene-Related Peptide; D019342:Acetic Acid