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

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.

Author information

1
Division of Urologic Surgery, Department of Surgery, Washington University School of Medicine, St Louis, MO, USA.
2
Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine, St Louis, MO, USA.

Abstract

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

PMID:
28581681
PMCID:
PMC5716917
[Available on 2018-10-01]
DOI:
10.1111/bju.13924
[Indexed for MEDLINE]

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