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). 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.

Diagnosis and Treatment of Interstitial Cystitis/Bladder Pain Syndrome: AUA Guideline Amendment

“…44 Shie et al injected 100 U in the posterior and lateral bladder walls with re-treatment every six months regardless of symptom status for a total of four treatments. 46 After treatment one but not treatments two through four, hydrodistension was performed. Patients were followed for two years with improvements in pain VAS, O'Leary-Sant scores and frequency restored with each treatment.…”

CUA guideline: Diagnosis and treatment of interstitial cystitis/ bladder pain syndrome

“…[184][185][186][187] The duration (approximately 9-10 months) 186 and strength of response seem to be maintained with repeat injections and rate of adverse events low.…”

Down Regulation of Vascular Endothelial Growth Factor Is Associated With Decreased Inflammation After Intravesical OnabotulinumtoxinA Injections Combined With Hydrodistention for Patients With Interstitial Cystitis—Clinical Results and Immunohistochemistry Analysis

“…5 Previous study demonstrated the degree of glomerulations decreases after repeated onabotulinumtoxinA injection. 17 Although the actual mechanism for this onabotulinumtoxinA effect on angiogenesis is unknown, it is important to elucidate which signal molecules are responsible for the regulation of angiogenesis after onabotulinumtoxinA treatment. The glomerulations and vascular permeability of IC/BPS bladder tissues seem to be because of inflammatory stimulation.…”