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Validation of peripheral CGRP signaling as a target for the treatment of pain in chronic pancreatitis

Award Number: R01DK123138
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Abstract Chronic pancreatitis remains a common and challenging clinical syndrome. Its cardinal feature, pain, has been difficult to treat effectively despite a multitude of empirical therapeutic approaches often leading to opioid addiction. Our laboratory has been actively pursuing the molecular pathogenesis of pain in pancreatitis for over a decade. In the process, we have established highly useful and relevant rodent models of CP and gained valuable insight into the contribution of specific molecules, such as nerve growth factor, NGF and transforming growth factor beta (TGF ). These molecules appear to be acting by a common effector and our preliminary data implicates calcitonin-gene related peptide (CGRP). CGRP has been classically thought to mediate pain by its role as a neurotransmitter relaying signals to second order neurons in the spinal cord (i.e. a central role) and in the case of migraine specifically, as a potent vasodilator. Recent developments in the treatment of migraine have increased interest in anti-CGRP strategies for pain. However, many questions about the mechanisms of action remain. Our overall hypothesis in this proposal is that peripheral CGRP is a major mediator of peripheral nociceptive sensitization in chronic pancreatitis and that peripherally restricted anti-CGRP treatment is an efficient and sufficient approach for pain in this condition. We will attempt to prove this hypothesis, using a comprehensive multidisciplinary approach encompassing molecular, electrophysiological and behavioral assays. The significance of this proposal is that if will validate CGRP as a therapeutic target, opening up the possibility for new non-addictive therapies in many other chronic painful disorders that may be inflammatory in origin.


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 = -$832,308 )
2025	2019	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	10/1/2024	NEW	-$71,403
2025	2019	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	2	10/1/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$280,533
2025	2019	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	10/1/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$480,373
														Subtotal = -$832,308

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2019	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	2	9/23/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$578,913
2024	2019	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	11/23/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2019	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	9/23/2024	NEW	-$578,913
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2019	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	5/10/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$338,079
2023	2019	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	5/9/2023	NEW	-$338,079
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2019	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/18/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/10/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2019	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/11/2020	NEW	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $2,266,058 )
2019	2019	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/20/2019	NEW	$2,266,058
														Subtotal = $2,266,058

Grand Total All Awards = $1,433,750

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Validation of peripheral CGRP signaling as a target for the treatment of pain in chronic pancreatitis

Award Number: R01DK123138

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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