Low energy shock wave-delivered intravesical botulinum neurotoxin-A potentiates antioxidant genes and inhibits proinflammatory cytokines in rat model of overactive bladder.

PURPOSE: To study the effect of intravesical instillation of botulinum neurotoxin-A (BoNT-A) combined with low energy shock wave (LESW) for treatment of overactive bladder (OAB) in a rat model and to investigate its effect on the associated inflammatory and oxidative stress process. MATERIAL AND METHODS: Forty rats were subdivided into four equal groups: normal control group, OAB group, LESW group, and BoNT-A plus LESW group. Cystometrogram (CMG) changes and histopathological changes in the bladder mucosa were assessed in the different groups. Oxidative stress markers (malondialdehyde [MDA] and superoxide dismutase [SOD]) and proinflammatory cytokines (tumor necrotic factor-α [TNF-α] and interleukin-6 [IL-6]) were compared among groups. RESULTS: BoNT-A plus LESW group showed statistically significant lower amplitude (p = .001) and lower frequency of detrusor contractions (p = .01) compared to LESW, which showed no statistically significant difference in comparison to the OAB group. Also, the combined group significantly reduced submucosal edema and inflammatory cell infiltrate scores compared to all groups (p < .05). LESW was associated with 42% reduction of MDA expression while, LESW plus BoNT-A decreased it by 68% (p < .001). Also, LESW and LESW plus BoNT-A increased SOD expression by 43% and 75%, respectively (p < .001). LESW plus BoNT-A was associated with statistically significant lower expression of TNF-α and IL-6 expression by 37% and 66% in comparison to LESW group (p = .001). CONCLUSION: Intravesical instillation of BoNT-A plus LESW is an effective method for increasing the urothelial permeability to BoNT-A and enhancing its therapeutic effect against OAB in rat model through the expression of a substantial anti-inflammatory and antioxidative stress effect.

Delivery of intravesical botulinum toxin A using low-energy shockwaves in the treatment of overactive bladder: A preliminary clinical study.

Objective: To evaluate the efficacy and safety of botulinum toxin A (BoNT-A) instillation in the bladder under the effect of low-energy shockwaves (LESWs) for the treatment of refractory idiopathic overactive bladder (OAB). Patients and methods: A preliminary clinical study was conducted, including 15 patients with refractory OAB, between September 2016 and July 2017. Intravesical instillation of 100 IU of BoNT-A was done followed by LESWs (3000 shocks over 10 min) exposure to the supra-pubic area. Patients were followed-up by urine analysis, urine culture, post-void residual urine volume (PVR), and Overactive Bladder Symptom Score (OABSS) at 1, 2 and 3 months. Results: There were statistically significant improvements in all OABSS domains and the total score after 1 and 2 months of treatment (P < 0.05). Whereas, only the nocturia domain remained significantly improved after 3 months (P = 0.02). There was no significant increase in PVR throughout the study period (P > 0.05) and none of the patients required clean intermittent catheterisation. Two, two and three patients developed urinary tract infections after 1, 2 and 3 months, respectively. Conclusion: Intravesical instillation of BoNT-A and LESWs is safe and effective method for the treatment of refractory OAB with a durable response for 2 months. Abbreviations: BoNT-A: botulinum toxin A; CIC: clean intermittent catheterisation; DO: detrusor overactivity; LESWs: low-energy shockwaves; OAB: overactive bladder; OABSS: Overactive Bladder Symptom Score; Qmax: maximum urinary flow rate; QoL: quality of life; UUI: urgency urinary incontinence.