# Regulation of pelvic pain and micturition reflex by VEGF in urological chronic pelvic pain syndrome

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $233,250

## Abstract

PROJECT SUMMARY
 Urological Chronic Pelvic Pain Syndrome (UCPPS) is a complex and multifactorial disorder characterized
by voiding and/or sexual dysfunction, visceral hyperalgesia, and chronic pelvic pain (CPP). Previous animal
studies from our laboratory established that peripheral neurogenic inflammation together with central
sensitization play a role in generation and maintenance of UCPPS symptoms. Recent study from the MAPP
network confirmed that VEGF could be one of the potential urinary biomarkers of UCPPS. Specifically, patients
with UCCPS had significantly higher levels of urinary VEGF and VEGF receptors than healthy controls.
Additionally, pain severity was significantly associated with increased urinary VEGF suggesting that it may serve
as a clinically useful diagnostic marker for UCPPS. Despite this novel clinical data, the sites and mechanisms of
VEGF action in the CNS centers controlling micturition, effects on excitability of peripheral and central neurons
innervating the lower urinary tract (LUT) are still unknown. Therefore, demonstration of mechanistic involvement
of VEGF in bladder pain and voiding dysfunction would provide scientific justification and “proof-of-concept” data
for designing clinical trials of anti-VEGF treatments to alleviate LUTS and bladder pain in UCPPS. While the role
of VEGF in angiogenesis has been previously well established, much less is known about its participation in
neurogenesis of visceral pain. We were the first group to provide direct evidence that intravesical instillation of
VEGF in mice promoted a significant increase in density of both sensory and motor nerves, which was associated
with urodynamically recorded detrusor overactivity and enhanced abdominal sensitivity. Current application
builds upon our initial findings, and is focused on determining the mechanisms by which VEGF modulates neural
plasticity of bladder peripheral and spinal neurons innervating the lower urinary tract. It will also explore potential
cross-effects of the VEGF-activated bladder nociceptive (pain-associated) pathways with the micturition reflex,
as observed in patients with UCPPS. Additional studies will test pharmacological approaches using available
VEGF neutralizing antibodies to evaluate their potential to limit pain sensation and restore bladder function using
translational animal models of bladder pain and voiding dysfunction. Overall, the study will result in novel,
interpretable data that expands recent MAPP studies in a hypothesis-driven complementary fashion, and will fill
the knowledge gap necessary for the development of individualized therapeutic approaches for patients with
UCPPS.

## Key facts

- **NIH application ID:** 9986762
- **Project number:** 5R01DK121506-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Anna P Malykhina
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $233,250
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986762

## Citation

> US National Institutes of Health, RePORTER application 9986762, Regulation of pelvic pain and micturition reflex by VEGF in urological chronic pelvic pain syndrome (5R01DK121506-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9986762. Licensed CC0.

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