# Contribution of Stress Induced Autonomic and Urothelial Dysregulation to IC/BPS

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $701,858

## Abstract

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic, painful condition associated with urinary
frequency and urgency for which there are no proven etiologies and no effective treatments. Evidence supports
a role for emotional stress in the exacerbation (and possibly development) of generalized pain syndromes such
as IC/BPS as well as micturition disorders. Recent analysis of a patient cohort by the MAPP (multidisciplinary
approach for the study of pelvic pain) network has confirmed robust differences between individuals with
IC/BPS and healthy controls in psychosocial variables and current and lifetime stress. Although the underlying
mechanisms mediating the impact of stress on pain are not well understood, recent evidence shows that
chronic stress and bladder dysfunction in IC/BPS may be related to autonomic (adrenergic) dysregulation that
influences nociceptive signaling. Our preliminary data have provided evidence for stress-induced autonomic
modulation of peripheral targets and mitochondrial functions that are likely to play a role in bladder pain. Taken
together, our overall hypothesis is that chronic stress induces autonomic and mitochondrial
dysregulation and leads to changes in urothelial-neural signaling influencing voiding and pain
behavior. Our research teams will use a multidisciplinary approach including molecular biology, measurement
of mitochondrial bioenergetics, electrophysiology and imaging to study the effects of psychological stress in our
validated rat chronic water avoidance or WAS model. In Aim #1, we will show that chronic stress increases
adrenergic signaling resulting in mitochondrial dysfunction that causes the observed breakdown in the UT
barrier. We will measure water and urea permeability and use morphological tools to examine how chronic
stress impairs urothelial (UT) regeneration. In Aim #2, we will show increased sympathetic outflow from chronic
stress alters UT memory modulated by altered mitochondrial signaling using functional assays (bioenergetics;
Ca+2 imaging; measurement of mitochondrial ROS) and molecular approaches. In Aim #3 we will show that
chronic stress induces afferent hyperexcitability and spinal cord glial cell activation producing symptom
equivalents in IC/BPS. We will examine the distribution and activity of bladder afferents and use genetic tools
(designer receptors exclusively activated by designer drugs- DREADDs) to block microglial activation and
correlate with changes in cellular and functional visceral responses. Of great importance to this project, as part
of the ancillary MAPP network we will have a unique opportunity for translational studies. Having access to
MAPP resources including patient phenotypes and blood samples will further strengthen the clinical relevance
of our findings in the animal model. Findings in our animal model will inform studies in the human and may
guide biomarker discovery. In sum, our intriguing preliminary data combined with our extensive experti...

## Key facts

- **NIH application ID:** 9957096
- **Project number:** 5R01DK115476-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** LORI A BIRDER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $701,858
- **Award type:** 5
- **Project period:** 2018-08-20 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9957096

## Citation

> US National Institutes of Health, RePORTER application 9957096, Contribution of Stress Induced Autonomic and Urothelial Dysregulation to IC/BPS (5R01DK115476-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9957096. Licensed CC0.

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