Wednesday, April 2, 2025 4/2/2025

Investigating the Neural Circuits of Itch

Award Number: R01AR063772
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Investigating the Neural Circuits of Itch - Abstract Chronic itch severely diminishes quality of life. Although several neuronal populations that are important for itch have been identified, we lack a population-level view of the neurons that detect itch stimuli in the dorsal root ganglia (DRG), integrate itch in the dorsal horn, and convey itch to the brain. Moreover, although kappa opioid receptor (KOR) agonists inhibit itch, we do not yet have a clear understanding of the neural basis of the inhibition of itch. We propose to bridge these critical gaps in knowledge with 2-photon (2P) Ca2+ imaging of neural populations that are engaged in response to itch and those that are inhibited by KOR agonists. A network view of how pruritic information is initially integrated—and where KOR agonists act to inhibit this circuitry—will provide key insight into the neural coding of itch, and may elucidate new avenues for treatment. Here, we propose to use 2P Ca2+ imaging in the ex vivo somatosensory preparation to define the neurons that are engaged by three types of disease-relevant itch: urticaria from mass cell degranulation, the AEW model of dry skin itch, and the SADBE model of contact dermatitis. In Aim 1 we will characterize the DRG neurons that mediate itch; in Aim 2 we will characterize the corresponding responses of spinal excitatory neurons and spinal projection neurons; and in Aims 3 we will analyze how this pattern of activity is altered in the presence of a KOR agonist, which inhibits itch. Overall, we will test the hypothesis that distinct types of itch engage common excitatory interneurons and common spinal output neurons, and that KOR agonists reduce activity in one or more of these populations, including spinal output neurons. These experiments will provide new insight into the neural circuits that mediate disease-relevant itch and how this circuitry can be inhibited by KOR agonists through a population view of the neurons that detect itch in the periphery, integrate itch in the dorsal horn, and convey itch to the brain.


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 = $576,255 )
2025	2025	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	13	3/3/2025	NON-COMPETING CONTINUATION	$576,255
2025	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	11	1/21/2025	COMPETING CONTINUATION	$7,063
2025	2022	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	10	1/21/2025	NON-COMPETING CONTINUATION	-$7,063
														Subtotal = $576,255

Issue Date FY: 2024 ( Subtotal = $621,076 )
2024	2024	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	12	3/11/2024	NON-COMPETING CONTINUATION	$576,255
2024	2024	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	12	6/14/2024	NON-COMPETING CONTINUATION	$44,821
														Subtotal = $621,076

Issue Date FY: 2023 ( Subtotal = $638,349 )
2023	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	11	4/10/2023	COMPETING CONTINUATION	$638,349
2023	2022	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	10	3/31/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $638,349

Issue Date FY: 2022 ( Subtotal = $459,239 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	10	1/27/2022	NON-COMPETING CONTINUATION	$417,490
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	10	5/11/2022	NON-COMPETING CONTINUATION	$41,749
														Subtotal = $459,239

Issue Date FY: 2021 ( Subtotal = $652,466 )
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	9	6/30/2021	NON-COMPETING CONTINUATION	$48,964
2021	2021	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	9	1/28/2021	NON-COMPETING CONTINUATION	$603,502
														Subtotal = $652,466

Issue Date FY: 2020 ( Subtotal = $764,664 )
2020	2020	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	8	3/2/2020	SUPPLEMENT FOR EXPANSION	$232,060
2020	2020	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	8	1/23/2020	NON-COMPETING CONTINUATION	$479,343
2020	2020	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	8	3/31/2020	NON-COMPETING CONTINUATION	$53,261
2020	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	003	7	6/22/2020	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $764,664

Issue Date FY: 2019 ( Subtotal = $463,158 )
2019	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	7	2/8/2019	NON-COMPETING CONTINUATION	$430,871
2019	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	7	7/15/2019	SUPPLEMENT FOR EXPANSION	$32,287
														Subtotal = $463,158

Issue Date FY: 2018 ( Subtotal = $441,960 )
2018	2018	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	3/9/2018	COMPETING CONTINUATION	$441,960
2018	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	5	5/15/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $441,960

Issue Date FY: 2017 ( Subtotal = $324,063 )
2017	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	1/31/2017	NON-COMPETING CONTINUATION	$291,656
2017	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	5	6/14/2017	NON-COMPETING CONTINUATION	$32,407
														Subtotal = $324,063

Issue Date FY: 2016 ( Subtotal = $324,063 )
2016	2016	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	1/25/2016	EXTENSION WITH OR WITHOUT FUNDS	$324,063
														Subtotal = $324,063

Issue Date FY: 2015 ( Subtotal = $324,063 )
2015	2015	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	1/21/2015	NON-COMPETING CONTINUATION	$324,063
														Subtotal = $324,063

Issue Date FY: 2014 ( Subtotal = $324,063 )
2014	2014	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	1/24/2014	NON-COMPETING CONTINUATION	$291,656
2014	2014	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	5/21/2014	NON-COMPETING CONTINUATION	$25,925
2014	2014	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	2	6/6/2014	NON-COMPETING CONTINUATION	$6,482
														Subtotal = $324,063

Issue Date FY: 2013 ( Subtotal = $324,063 )
2013	2013	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	2/12/2013	NEW	$324,063
														Subtotal = $324,063

Grand Total All Awards = $6,237,482

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Investigating the Neural Circuits of Itch

Award Number: R01AR063772

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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