# Central Sensitization and Psychosocial Impacts on Overactive Bladder

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $467,430

## Abstract

PROJECT SUMMARY
Non-neurogenic overactive bladder (OAB) (i.e. urinary urgency, with or without urgency urinary incontinence,
frequency, and nocturia) affects 1 in 7 U.S. men and women. It can be difficult to treat effectively, and the present
approach is one-size-fits-all, trial-and-error, in large part because the etiology of OAB remains unclear. A
substantive body of animal and ex vivo research implicates increased afferent activity and altered CNS
processing of excitatory signals in OAB pathophysiology, contributing to bladder hypersensitivity. However,
clinical characteristics that may reflect a bladder hypersensitivity state are poorly recognized and thus
phenotyping OAB based on afferent pathophysiologic mechanisms, which would be crucial for individualized
OAB care, has remained elusive. In response, we hypothesize that central sensitization (CS) is a
pathophysiologic mechanism underlying OAB in certain individuals, which might explain the bladder
hypersensitivity proposed in OAB. Findings from our preliminary work demonstrating elevated temporal
summation to pain (i.e. primary marker for CS indexed with quantitative sensory testing, TSP) in female OAB
patients appear to support this. Yet, we still know very little about how CS manifests in OAB, including how
relevant it may be for men with OAB. Therefore, we now propose that CS not only contributes to bladder
sensitivity, but also to psychosocial burdens, specifically increased negative affect (which is a frequent finding
both individuals with CS-mediated conditions and OAB), which then impacts bladder symptoms. We will test this
hypothesis with a sample of 200 men and women with OAB and 60 non-OAB controls, using a highly innovative,
interdisciplinary approach. Aim 1 identifies phenotypic features characteristic of CS in OAB, including greater
central sensory sensitivity, elevated psychosocial factors, co-morbidity with chronic pain conditions, and greater
urinary symptoms. Because CS links to OAB have not previously been examined in men, we will test for sex
differences in CS-related phenotypes. Aim 2 will directly test, for the first time, the effects of CS on bladder
sensitivity in OAB. Aim 3 will examine whether CS moderates the day-to-day negative affective influences on
OAB symptoms using a state-of-the-art ecological momentary assessment approach. When completed, we
expect to be able to identify OAB individuals with a mechanism-based phenotype (CS-associated OAB) defined
by signature mechanistic and phenotypic features for the first time. We anticipate that individuals with this CS-
OAB association, likely because of the high psychosocial impact and CS-mediated hypersensitivity, will be more
difficult to treat using standard OAB interventions (i.e. OAB medications) and may require multimodal or
advanced therapy. This will be assessed with future intervention studies to measure individualized OAB
treatment outcomes based on underlying CS mechanisms and determine causality of this O...

## Key facts

- **NIH application ID:** 10890812
- **Project number:** 5R01DK128293-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Lindsey Colman McKernan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $467,430
- **Award type:** 5
- **Project period:** 2021-09-24 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890812

## Citation

> US National Institutes of Health, RePORTER application 10890812, Central Sensitization and Psychosocial Impacts on Overactive Bladder (5R01DK128293-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10890812. Licensed CC0.

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