title: Immunohistochemical evidence suggests repeated intravesical application of botulinum toxin A injections may improve treatment efficacy of interstitial cystitis/bladder pain syndrome.
abstract: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: 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).
  
  
  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.
authors.affiliation: Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan.
authors.forename: Jia-Heng
authors.initials: JH
authors.lastname: Shie
authors.forename: Hsin-Tzu
authors.initials: HT
authors.lastname: Liu
authors.forename: Yu-Syuan
authors.initials: YS
authors.lastname: Wang
authors.forename: Hann-Chorng
authors.initials: HC
authors.lastname: Kuo
mesh_terms: D000283:Administration, Intravesical; D001707:Biopsy, Needle; D015153:Blotting, Western; D019274:Botulinum Toxins, Type A / Q000627:therapeutic use*; D015331:Cohort Studies; D018856:Cystitis, Interstitial / Q000150:complications / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008875:Middle Aged; D010147:Pain Measurement; D011446:Prospective Studies; D011788:Quality of Life; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014563:Urodynamics
chemical_list: D019274:Botulinum Toxins, Type A