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A new animal model for stress-induced transition from acute to chronic pain

Award Number: K02DE023551
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/13/2014
PERIOD OF PERFORMANCE END DATE: 06/30/2022

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A new animal model for stress-induced transition from acute to chronic pain - DESCRIPTION (provided by applicant): The transition from acute to chronic pain is likely to result from a complex combination of mechanisms. It is important to develop a useful preclinical animal model that can replicate the complexity of the human condition. Previous studies have shown that psychosocial and socio-environmental factors are involved in the development of chronic postsurgical pain. In our preliminary studies, we found that forced swim stress significantly enhances plantar incision-induced �-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor phosphorylation and greatly prolongs plantar incision-induced pain, but forced swim stress alone does not produce pain behaviors; we also found that targeted mutation of AMPA receptor GluA1 phosphorylation site Ser831 significantly inhibits stress-induced prolongation of incisional pain. Thus, stress may induce pain transition by regulating AMPA receptor phosphorylation. Recently, we further found that forced swim stress significantly increases GluA1 membrane surface expression and GluA2 internalization and thereby enhances synaptic AMPA receptor switch from Ca2+-impermeable (GluA2-containing) to Ca2+-permeable (GluA2-lacking) in the spinal dorsal horn neurons. This switch will increase Ca2+ influx and further activate Ca2+-dependent protein kinases, thereby promoting AMPA receptor phosphorylation and other phosphorylation-triggered activities. This positive feedback loop may contribute to the molecular mechanisms that underlie stress- induced pain transition. Therefore, we hypothesize that regulation of AMPA receptor phosphorylation and phosphorylation-triggered synaptic AMPA receptor switch from Ca2+-impermeable to Ca2+-permeable contribute to a key mechanism by which stress induces the transition from acute to chronic pain. To address this central hypothesis, we will combine plantar incision with different levels of stress to develop a new animal model to study pain transition (specific aim 1), we will investigate stress-produced regulation of AMPA receptor activities (phosphorylation, trafficking, synaptic targeting, and subunit composition change) in our pain transition model (specific aim 2), and we will investigate the role of phosphorylation-triggered switch of AMPA receptors from Ca2+-impermeable to Ca2+-permeable in stress-induced pain transition (specific aim 3). The overall goal of this proposal is to develop a new animal model for pain transition study and provide critical evidence to characterize the pain transition model. The proposed studies will demonstrate the role of stress- produced AMPA receptor regulation in the transition from acute to chronic pain and shed new light on the pathogenesis of chronic postsurgical 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: 2023 ( Subtotal = -$74 )
2023	2018	TEXAS A & M UNIVERSITY SYSTEM HEALTH SCIENCE CENTER	6003 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Oral Diseases and Disorders Research	000	6	1/20/2023	NON-COMPETING CONTINUATION	-$74
														Subtotal = -$74

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2018	TEXAS A&M UNIVERSITY SYSTEM, THE	8441 RIVERSIDE PARKWAY BLDG 1 STE 3100	BRYAN	TX	77807	BRAZOS	USA	Oral Diseases and Disorders Research	000	6	3/11/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	TEXAS A&M UNIVERSITY SYSTEM, THE	8441 RIVERSIDE PARKWAY BLDG 1 STE 3100	BRYAN	TX	77807	BRAZOS	USA	Oral Diseases and Disorders Research	000	6	3/20/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $112,713 )
2018	2018	TEXAS A&M UNIVERSITY SYSTEM,THE	200 TECHNOLOGY WAY, STE 2079	COLLEGE STATION	TX	77845	BRAZOS	USA	Oral Diseases and Disorders Research	000	6	4/27/2018	NON-COMPETING CONTINUATION	$112,713
														Subtotal = $112,713

Issue Date FY: 2017 ( Subtotal = $112,713 )
2017	2017	TEXAS A&M UNIVERSITY SYSTEM,THE	200 TECHNOLOGY WAY, STE 2079	COLLEGE STATION	TX	77845	BRAZOS	USA	Oral Diseases and Disorders Research	000	5	5/12/2017	NON-COMPETING CONTINUATION	$112,713
														Subtotal = $112,713

Issue Date FY: 2016 ( Subtotal = $112,713 )
2016	2016	TEXAS A&M UNIVERSITY HEALTH SCIENCE CENTER	301 Tarrow	COLLEGE STATION	TX	77840	BRAZOS	USA	Oral Diseases and Disorders Research	000	4	5/11/2016	NON-COMPETING CONTINUATION	$112,713
														Subtotal = $112,713

Issue Date FY: 2015 ( Subtotal = $112,713 )
2015	2015	TEXAS A&M UNIVERSITY HEALTH SCIENCE CENTER	301 Tarrow	COLLEGE STATION	TX	77840	BRAZOS	USA	Oral Diseases and Disorders Research	000	3	6/15/2015	NON-COMPETING CONTINUATION	$112,713
														Subtotal = $112,713

Issue Date FY: 2014 ( Subtotal = $112,713 )
2014	2014	JOHNS HOPKINS UNIVERSITY	1101 E 33RD STREET, STE-C-210	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Oral Diseases and Disorders Research	000	1	6/24/2014	NEW	$112,713
2014	2014	TEXAS A&M UNIVERSITY HEALTH SCIENCE CENTER	301 Tarrow	COLLEGE STATION	TX	77840	BRAZOS	USA	Oral Diseases and Disorders Research	001	2	9/9/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$112,713
2014	2014	JOHNS HOPKINS UNIVERSITY	1101 E 33RD STREET, STE-C-210	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Oral Diseases and Disorders Research	002	1	9/9/2014	NEW	-$112,713
														Subtotal = $112,713

Grand Total All Awards = $563,491

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A new animal model for stress-induced transition from acute to chronic pain

Award Number: K02DE023551

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/13/2014

PERIOD OF PERFORMANCE END DATE: 06/30/2022

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