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

Abstract

To measure the expression of vascular endothelial growth factor (VEGF) in bladder tissue and improvement of clinical symptoms and inflammatory biomarkers after repeated onabotulinumtoxinA injections in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Twenty-one patients with IC/BPS received 4 sets of intravesical 100-U onabotulinumtoxinA injections combined with hydrodistention. Assessments at baseline and 6 months after each treatment included O'Leary-Sant Symptom Score, bladder pain visual analog scale, functional bladder capacity (FBC), grade of glomerulations under cystoscopic hydrodistention, and urodynamic parameters. The bladder specimens at baseline and at the fourth treatment were investigated by western blotting for the expression of VEGF, Bcl-2-associated X protein (Bax), and phospho-p38 (p-p38), and immunohistochemistry staining for apoptotic and mast cell activity. Six women with genuine stress urinary incontinence served as controls for comparison. The measured immunohistochemical parameters were significantly higher in patients with IC/BPS than the controls. Statistically significant decrease in the expression of VEGF was noted in patients treated with repeated onabotulinumtoxinA injections compared with baseline (0.83 ± 0.28 vs 1.00; P = .016). The apoptotic cell count (0.86 ± 1.00 vs 1.76 ± 1.69; P = .026) and mast cell activity (1.81 ± 2.29 vs 5.82 ± 4.97; P = .009) were also reduced. Significant increases in FBC and global response assessment score were also observed after onabotulinumtoxinA treatment; however, except for mast cell activity, VEGF expression and apoptotic cell count were still significantly higher than the controls. Increased VEGF was associated with bladder inflammation and smaller FBC in patients with IC/BPS and decreased after repeated onabotulinumtoxinA injections and hydrodistention, suggesting VEGF plays an important role in the pathogenesis of IC/BPS.