Anti-vascular endothelial growth factor treatment decreases bladder pain in cyclophosphamide cystitis: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network animal model study

BJU Int. 2017 Oct;120(4):576-583. doi: 10.1111/bju.13924. Epub 2017 Jun 29.


Objective: To investigate whether treatment with anti-vascular endothelial growth factor (VEGF)-neutralizing antibodies can reduce pain and voiding dysfunction in the cyclophosphamide (CYP) cystitis model of bladder pain in mice.

Materials and methods: Adult female mice received anti-VEGF-neutralizing antibodies (10 mg/kg i.p. B20-4.1.1 VEGF mAb) or saline (control) pre-treatment, followed by CYP (150 mg/kg i.p.) 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.

Results: Systemic anti-VEGF-neutralizing antibody treatment significantly reduced the pelvic nociceptive response to CYP cystitis compared with 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) using von Frey filaments at 5 h post-CYP administration (P = 0.004); however, by 48 h and 96 h post-CYP administration, pelvic hypersensitivity had reduced by 54% and 47%, respectively, compared with the 5 h post-CYP administration time point, and were no longer significantly different from 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.

Conclusion: Systemic blockade of VEGF signalling 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.

Keywords: bladder pain; cyclophosphamide cystitis; interstitial cystitis; vascular endothelial growth factor anti-VEGF.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cyclophosphamide / adverse effects*
  • Cystitis / chemically induced
  • Cystitis / physiopathology*
  • Disease Models, Animal
  • Female
  • Follow-Up Studies
  • Mice
  • Mice, Inbred C57BL
  • Pain / drug therapy*
  • Pain / etiology
  • Pain / physiopathology
  • Pain Measurement
  • Pelvic Pain / drug therapy*
  • Pelvic Pain / etiology
  • Pelvic Pain / physiopathology
  • Random Allocation
  • Reference Values
  • Severity of Illness Index
  • Treatment Outcome
  • Urination
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / pharmacology


  • Vascular Endothelial Growth Factor A
  • Cyclophosphamide