# Afferent and urothelial plasticity underlying bladder sensitization in prostatic inflammation

> **NIH NIH U54** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $219,983

## Abstract

Project Summary/Abstract
Project 1 of the program is entitled "Afferent and urothelial plasticity underlying bladder
sensitization in prostatic inflammation" (Project Leader: Naoki Yoshimura, Department of
Urology). Prostatic inflammation is considered to be an important component of benign
prostate hyperplasia (BPH) in addition to androgen-mediated ``static'' prostate enlargement and
‘‘dynamic’’ α-adrenoceptor–mediated muscle tension. Previous studies also suggest that
asymptomatic prostatic inflammation associated with the development of histological BPH in
involved in the emergence of lower urinary tract symptoms (LUTS). Thus, the following three
key aims utilize unique and innovative expertise available in Pittsburgh to identify the detailed
mechanisms of bladder overactivity, urothelial dysfunction and afferent hyperexcitability after
prostatic inflammation, which reportedly contribute to lower urinary tract symptoms (LUTS) in
patients with benign prostatic hyperplasia (BPH). We will also aim to determine whether
treatments of local NGF antisense application, COX-2 inhibition or 5α-reductase inhibition can
reverse the pathological processes initiated by prostatic inflammation.
 In this application, we propose to extend our previously NIDDK P20 research project
(DK090919, PI: Wang) entitled “University of Pittsburgh Planning Center for Benign Prostate
Hyperplasia Research”, by critical evaluation of new mechanisms and development of
innovative treatment options for male LUTS induced by prostatic inflammation. For this
purpose, we will utilize an animal model of prostatic inflammation induced by local injection of
formalin, , which was developed in our previously funded P20 project. First, we will study the
changes in bladder function and functional/molecular properties of afferent neurons innervating
the prostate and/or bladder to identify the role of prostate-to-bladder afferent cross sensitization
in the development of LUTS due to prostatic inflammation. Secondly, we will examine whether
prostatic inflammation induces bladder urothelial dysfunction, which also contributes to LUTS
development. Lastly, we will seek to elucidate whether intravesical application of NGF
antisense conjugated with liposomes targeting urothelial NGF production, COX-2 inhibitors
(celecoxib) or 5α-reductase inhibitors (finasteride) can reverse functional and molecular
changes in the bladder, urothelium and prostate/bladder afferent pathways initiated by prostatic
inflammation in the rat model.
 The long-term objectives of the research program are to identify new and effective targets
and methods for the treatment of LUTS associated with BPH. Project 1 will maximize the uses
of the resources of Administrative and Tissue Cores, and has strong synergy with other projects.

## Key facts

- **NIH application ID:** 10002343
- **Project number:** 5U54DK112079-05
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** NAOKI YOSHIMURA
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $219,983
- **Award type:** 5
- **Project period:** 2016-09-22 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10002343

## Citation

> US National Institutes of Health, RePORTER application 10002343, Afferent and urothelial plasticity underlying bladder sensitization in prostatic inflammation (5U54DK112079-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10002343. Licensed CC0.

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