Immunohistochemical evidence suggests repeated intravesical application of botulinum toxin A injections may improve treatment efficacy of interstitial cystitis/bladder pain syndrome - Abstract

A single set of botulinum toxin A (BoNT-A) injections relieves clinical symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS), but lacks long-term effect.

An inadequate anti-inflammatory effect is likely to cause treatment failure. The study shows that chronic inflammation and apoptotic signalling molecules are significantly reduced after repeated intravesical BoNT-A injection in patients with IC/BPS. It also shows that repeated BoNT-A injections are necessary to achieve greater success in the treatment of IC/BPS.

OBJECTIVE:To investigate the mechanisms of action of botulinum toxin A (BoNT-A) treatment on interstitial cystitis/bladder pain syndrome (IC/BPS).

PATIENTS AND METHODS:A total of 23 women with IC/BPS who received single intravesical BoNT-A injection were studied. Among them, 11 received three repeated injections every 6 months to improve their symptoms. Bladder biopsy was obtained before each BoNT-A injection and the clinical symptoms and urodynamic variables were recorded.  Immunohistochemical (IHC) staining for TUNEL and mast cell activity, and western blotting analysis of tryptase, cytokines, Bax and phospho-p38 (p-p38) were carried out. We compared the clinical results and IHC data among baseline, single or repeated BoNT-A treatments.

RESULTS:Single BoNT-A injection improved clinical symptoms, pain score and daytime urinary frequency.  Mast cell activity and apoptotic cell count did not decrease significantly, while Bax and p-p38, but not tryptase, decreased significantly after a single BoNT-A injection.  The 11 patients who received three repeated BoNT-A injections had significantly lower pain scores than the remaining patients (mean [sd]: 5.80 [2.27] vs. 3.03 [2.30], P= 0), glomerulation degree (mean [sd]: 1.80 [1.06] vs. 1.20 [1.06], P= 0.026) and global response scores (mean [sd]: 0.30 [0.92] vs. 1.20 [1.06], P= 0) after treatment. Tryptase, Bax, p-p38 and apoptotic cell counts all decreased significantly. 25-kD synaptosomal-associated protein also decreased after BoNT-A treatments, which confirmed the therapeutic effect of repeated BoNT-A injections.

CONCLUSIONS: Chronic inflammation and apoptotic signalling molecules were significantly reduced after repeated BoNT-A injections in patients with IC/BPS. The IHC improvement was associated with clinical symptom improvement. Repeated BoNT-A injections are necessary to achieve a greater success rate in the treatment of IC/BPS.

Written by:
Shie JH, Liu HT, Wang YS, Kuo HC.   Are you the author?
Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan.

Reference: BJU Int. 2012 Sep 3. Epub ahead of print.
doi: 10.1111/j.1464-410X.2012.11466.x


PubMed Abstract
PMID: 22943596

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