# Urothelial Cells and Sensory Signaling

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2024 · $521,019

## Abstract

PROJECT SUMMARY
Urothelial cells play an active role in bladder physiology by responding to physical/chemical stimuli and
signaling to sensory neurons and other cell types in the bladder. Numerous bladder diseases affecting millions
of people, including overactive bladder, pain related to recurrent bladder infection, chemotherapeutic cystitis,
and bladder pain syndrome, have been suspected to disrupt urothelial sensory signaling, leading to
pathological changes to sensory signaling, including pain. While it has been accepted that urothelial cells play
a role in bladder sensory function, it is unclear how these cells contribute to the sensation of filling and how it is
altered under painful conditions. To unravel the role of urothelial cells in bladder nociception and sensory
dysfunction, we have developed a novel mouse model that allows for direct stimulation of urothelial cells using
optogenetics. We will functionally and molecularly identify the population of sensory neurons responding to
direct urothelial stimulation of sensory nerve activity in normal and inflammatory conditions. Identifying these
neurons may lead to more targeted therapies for treating visceral pain and sensory disorders associated with
epithelial dysfunction. We will also assess which brain areas increase activity with optogenetic urothelial
stimulation using functional magnetic resonance imaging and compare it to noxious and non-noxious
distension to understand better the sensory information relayed by urothelial cells to the central nervous
system. The results from these studies will allow us to understand better how urothelial cells contribute to
bladder interoception and nociception and under what conditions. Finally, we will examine the impact of
urothelial stimulation on voiding and nociceptive behaviors in freely moving mice before and after induction of
cystitis using wireless light delivery devices. These experiments will give us insight into the role of urothelial
sensory signals behaviorally. The project's overall goal is to evaluate and identify components of the
communication between urothelial cells, sensory neurons, and the brain. Further, we will investigate how this
signaling is changed under altered urothelial function. The results from this proposal will aid in furthering our
understanding of urothelial sensory neuron signaling in aspects of pain. Hopefully, this improved understanding
will lead to better therapeutic targets for bladder pain and other painful visceral disorders.

## Key facts

- **NIH application ID:** 10942380
- **Project number:** 1R01DK140233-01
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Aaron David Mickle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $521,019
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10942380

## Citation

> US National Institutes of Health, RePORTER application 10942380, Urothelial Cells and Sensory Signaling (1R01DK140233-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10942380. Licensed CC0.

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