To investigate whether treatment with anti-VEGF (vascular endothelial growth factor) neutralizing antibodies can reduce pain and voiding dysfunction in the cyclophosphamide (CYP) cystitis model of bladder pain in mice.
Adult female mice received anti-VEGF neutralizing antibodies (10 mg/kg intraperitoneal B20-4.1.1 VEGF mAb) or saline (control) pre-treatment, followed by CYP (150 mg/kg intraperitoneal) to induce acute cystitis. Pelvic nociceptive responses were assessed by applying von Frey filaments to the pelvic area. Spontaneous micturition was assessed using the void spot assay.
Systemic anti-VEGF neutralizing antibodies treatment significantly reduced the pelvic nociceptive response to CYP cystitis compared to control (saline). In the anti-VEGF pre-treatment group, there was a significant increase in pelvic hypersensitivity measured by the area under the curve (AUC) with von Frey filaments at 5 hours post-CYP (p=0.0035). However by 48 and 96 hours post-CYP, the pelvic hypersensitivity have reduced by 54% and 47% respectively compared to the 5 hours post-CYP time point, and were no longer significantly different from the baseline (p=0.22 and 0.17 respectively). There was no difference in urinary frequency and mean voided volume between the two pre-treatment groups.
Systemic blockade of VEGF signaling with anti-VEGF neutralizing antibodies was effective in reducing pelvic/bladder pain in the CYP cystitis model of bladder pain. Our data support the further investigation of the use of anti-VEGF antibodies to manage bladder pain or visceral pain. This article is protected by copyright. All rights reserved.
BJU international. 2017 Jun 05 [Epub ahead of print]
H Henry Lai, Baixin Shen, Pooja Vijairania, Zhang Xiaowei, Sherri K Vogt, Robert W Gereau
Division of Urologic Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO., Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine, St Louis, MO.