Login to Access Video or Poster Abstract: MP94-03
Sources of Funding: NIH/NIDDK MAPP (Multi-disciplinary Approach to the Study of Chronic Pelvic Pain) Research Network

Introduction

Vascular endothelial growth factor (VEGF) is a pleiotropic cytokine known for its angiogenesic activity. Clinical studies have shown that tissue and urinary levels of VEGF are elevated among patients with interstitial cystitis/bladder pain syndrome (IC/BPS). We investigated whether treatment with anti-VEGF neutralizing antibodies reduced pain and voiding dysfunction in the cyclophosphamide (CYP) cystitis model of bladder pain in mice.

Methods

Adult female mice received anti-VEGF neutralizing antibodies (10 mg/kg intraperitoneal B20-4.1.1 VEGF mAb) or saline (control) prior to receiving CYP (150 mg/kg intraperitoneal). Pelvic nociceptive responses were assessed 5, 48, and 96 hours later by applying von Frey filaments to the lower abdominal/pelvic area. Spontaneous micturition was assessed using the void spot assay. A second paradigm where anti-VEGF treatment was given after CYP cystitis was also investigated.

Results

Systemic anti-VEGF pre-treatment in mice prior to CYP-induced cystitis significantly reduced the pelvic nociceptive response compared to saline pre-treatment (control). As shown in the figure, pelvic hypersensitivity decreased significantly between 5 and 48 hours post-CYP in the anti-VEGF pre-treatment group (p=0.0051, n=7). By 96 hours post-CYP, pelvic hypersensitivity had decreased by 47.2% from its peak, and was no longer significantly different from the baseline level in mice pre-treated with anti-VEGF (p=0.17). In contrast, pelvic hypersensitivity remained elevated at 5, 48 and 96 hours in the saline pre-treatment group. There was no difference in urinary frequency and mean voided volume between the two groups at 5, 48, and 96 hours. In the second paradigm where anti-VEGF treatment was given after CYP cystitis has been established, pelvic hypersensitivity was still significantly increased at 96 hours compared to baseline (p=0.0007, n=7).

Conclusions

Administration of anti-VEGF neutralizing antibodies reduced pelvic/bladder pain in the CYP cystitis model of bladder pain compared to controls. Further investigation of the use of anti-VEGF antibodies to manage bladder pain or visceral pain in humans is warranted.

Funding

NIH/NIDDK MAPP (Multi-disciplinary Approach to the Study of Chronic Pelvic Pain) Research Network