# PACAP/PAC1 receptor signaling in micturition neurocircuits: effects of stress and injury/inflammation

> **NIH NIH R01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2024 · $293,920

## Abstract

(PLEASE KEEP IN WORD, DO NOT PDF)
Bladder Pain Syndrome (BPS)/ Interstitial Cystitis (IC) is a chronic pelvic pain disorder characterized by suprapubic, pelvic pain with at least one urinary symptom. Stress exacerbates symptoms of BPS/IC. Despite intense research, we lack understanding of how structural and functional changes in the micturition reflex are linked to BPS/IC and how stress exacerbates symptoms, thus impeding effective therapies. Expanding upon our previous collaborations, integrating our diverse scientific disciplines, and combining our unique laboratory strengths, we will use a repeated variate stress (RVS) and cyclophosphamide (CYP) injury/inflammation models to test the overall hypothesis that increases in urinary frequency and pelvic pain responses from stress- and injury-induced changes in central micturition and peripheral sensory circuits, respectively, reflect PACAP/PAC1 receptor-mediated signaling and neuroplasticity to engender a pro-excitatory state. Building from our previous work, we will assess how maladaptive intersections between the PACAP/PAC1R pathways may be contributory to stress-induced urinary bladder dysfunction and pelvic pain. Aim 1: To test whether RVS, in the absence of direct urinary bladder insults, induces changes in micturition reflexes that are associated with PACAP/PAC1R neurochemical plasticity in central neural circuits. Hypothesis: Our previous studies have demonstrated neuropeptide phenotypic plasticity, including changes in PACAP/PAC1R expression after stress challenges. Coordinate with these responses, we anticipate that RVS and CYP challenges will similarly result in central micturition pathway PACAP/PAC1R plasticity to alter voiding and pain responses. These studies are significant in the: (1) mechanistic insight gained of underlying structural and functional changes contributory to stress- and injury/inflammation-induced changes in voiding behavior and pelvic pain; (2) influence of psychological stress on central circuits underlying bladder function and pelvic sensation and (3) identification PACAP/PAC1 receptor-mediated signaling as a novel target for stress- and injury/inflammation-induced urinary bladder dysfunction and pelvic pain.

## Key facts

- **NIH application ID:** 10923973
- **Project number:** 5R01DK137815-02
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** SAYAMWONG E. HAMMACK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $293,920
- **Award type:** 5
- **Project period:** 2023-09-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10923973

## Citation

> US National Institutes of Health, RePORTER application 10923973, PACAP/PAC1 receptor signaling in micturition neurocircuits: effects of stress and injury/inflammation (5R01DK137815-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10923973. Licensed CC0.

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