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

Award Number: R01DK137815
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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PACAP/PAC1 receptor signaling in micturition neurocircuits: effects of stress and injury/inflammation - (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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $307,000 )
2025	2025	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT STREET	BURLINGTON	VT	05405	CHITTENDEN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	6/10/2025	NON-COMPETING CONTINUATION	$307,000
														Subtotal = $307,000

Issue Date FY: 2024 ( Subtotal = $293,920 )
2024	2024	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT STREET	BURLINGTON	VT	05405	CHITTENDEN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	8/7/2024	NON-COMPETING CONTINUATION	$293,920
2024	2023	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT STREET	BURLINGTON	VT	05405	CHITTENDEN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	10/12/2023	NEW	$0
														Subtotal = $293,920

Issue Date FY: 2023 ( Subtotal = $306,000 )
2023	2023	UNIVERSITY OF VERMONT & STATE AGRICULTURAL COLLEGE	85 S PROSPECT STREET	BURLINGTON	VT	05405	CHITTENDEN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/7/2023	NEW	$306,000
														Subtotal = $306,000

Grand Total All Awards = $906,920

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

Award Number: R01DK137815

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/15/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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