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

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) pretreatment, 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 pretreatment 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.National Institutes of Health [U01-DK-082315, K08-DK-094964]; National Natural Science Foundation of China [81400758]; China Scholarship Council [2013081110286]; Research Fund for the Doctoral Program of Higher Education [20120001120056]SCI(E)ARTICLE4576-58312