ANAHEIM, Calif. -- Expanding the urologic applications of botulinum toxin, two small clinical studies demonstrated significant symptom improvement in women with refractory interstitial cystitis.
ANAHEIM, Calif., May 21 -- Two small clinical studies demonstrated significant symptom improvement in women with refractory interstitial cystitis.
The studies, which expand the urologic applications of botulinum toxin, were reported here at the American Urological Association meeting by researchers from Germany and Taiwan.
In the larger of the two studies, a single injection of botulinum toxin led to statistically significant symptom relief in 24 of 29 patients (83%) at six weeks. In the second study, 14 of 19 patients reported significant improvement in pain, urinary frequency, and other symptoms after three months.
"Our results suggest that botulinum toxin A has an antinociceptive effect on bladder afferent pathways in patients with interstitial cystitis and gives symptomatic and functional improvement," concluded Stefan Carl, M.D., a urologist in Emmendingen, Germany, where the larger study was conducted. "No systemic side effects were observed during or after treatment, and in three patients major surgery was avoided."
Botulinum toxin has been used successfully in the treatment of urinary incontinence, Dr. Carl said. Experimental data from a somatic pain model suggests that the agent has an antinociceptive effect on chronic inflammatory pain, he noted.
Extending the investigation of the pain-relieving potential, Dr. Carl and his colleagues enrolled 29 interstitial cystitis patients whose symptoms had not responded to conventional treatments, including three patients scheduled for cystectomy.
Each patient received 500 MU of botulinum toxin in 3 ml of saline, administered submucosally through a rigid cystocopy at 20 to 25 sites in the trigone and bladder floor. Urodynamic assessments were performed before and after treatment.
Six weeks after treatment all but five patients reported significant improvement (p
Half the low-dose patients and all of the high-dose patients reported painful or difficult urination and a large postvoid residual volume during the first month after treatment, he noted, but the conditions had improved or resolved by three months.
Response to botulinum toxin correlated with declines in nerve growth factor (NGF) mRNA, which was elevated in all patients at baseline. NGF levels declined significantly in responders (p=0.002) but not in patients who did not meet criteria for response.
The studies are notable for the durability of treatment effect and for producing evidence of disease-state modification, commented Roger Dmochowski, M.D., professor of urologic surgery at Vanderbilt University Medical Center in Nashville.
"The syndrome is changing and less medication is being required to maintain the effect with botulinum toxin," said Dr. Dmochowski. "Disease-state modification is very specific. The other take-home message from these studies is the effect on bladder sensory mechanisms. For the interstitial cystitis public, I think we're starting to see some positive signal."
"Lastly," he said, "botulinum toxin mechanism at work appears to be complex. It's not just an effect on acetylcholine. Several other neurotransmitters appear to be involved and that probably explains why it affects sensation."