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Amygdala and Pain-Associated Mood Disorders

Award Number: R01MH105528
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2014
PERIOD OF PERFORMANCE END DATE: 11/30/2021

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Amygdala and Pain-Associated Mood Disorders - DESCRIPTION (provided by applicant): Chronic pain often leads to pathological mood changes and associated cognitive impairment. There is a fundamental need for development of better therapeutic approaches for both the pain and the comorbid mood disorders. Specific and detailed information about mechanisms causing mood changes in chronic pain is required for treatment advances. The central nucleus of the amygdala (CE) mainly consists of inhibitory GABAergic neurons. They coexpress several neuropeptides that may serve as co-transmitters and modulate aspects of pain and mood. Therefore, the CE inhibitory GABAergic neurons are likely to be a critical link between pain and mood. The long-term goal of my research is to establish new strategies for pharmaceutical development of psychotropic medications for treatment of mood disorders associated with chronic pain. The study objective in this proposal is to determine the mechanism by which GABA signaling in the amygdala modulates manifestations of anxiety, depression and memory impairment that develop during chronic pain, and to identify the specific brain targets of the CE GABA neurons. My central hypothesis is that the over-activity of specific CE GABAergic neuronal subpopulations, brought on by the increased nociceptive input during chronic pain, negatively affects emotional processing and induces depressive mood in susceptible individuals. The rationale for the proposed studies is that description of a new mechanism underlying development of mood disorders will provide opportunities for the development of new pharmacological strategies based on highly selective (potentially GABAergic) drugs, for both mood and pain. Three specific aims will be used to prove my hypothesis: 1) determine the relative contributions of amygdalar inhibitory subpopulations to the development of behavioral changes associated with pain; 2) assess the sequelae of increased amygdalar GABA activity on learning and memory during pain and 3) evaluate the long-term consequences of pain, after the pain is resolved, on pain associated behavior. I will use a pharmacological-genetic approach that allows spatial and temporal control of G-protein coupled receptor signaling in vivo to address the first two aims and I will use a newly developed technique for reversal of neuropathic injury to accomplish the last aim. Two collaborators will provide their expertise. The laboratory has the equipment and facilities required for this project. This contribution will be significant because it will aid the identifiction of specific, functionally distinct, neuronal groups in the amygdala and their role in the development of anxiety and depressed mood triggered by persistent pain. The proposed research is innovative because it has been designed specifically to evaluate the contribution of specific CE populations, as defined by their neurotransmitter expression, to pain generated anxiety and depressive mood.


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: 2022 ( Subtotal = -$26,849 )
2022	2019	ROSALIND FRANKLIN UNIVERSITY OF MEDICINE & SCIENCE	3333 GREEN BAY RD	NORTH CHICAGO	IL	60064	LAKE	USA	Mental Health Research Grants	000	5	7/15/2022	NON-COMPETING CONTINUATION	-$26,849
														Subtotal = -$26,849

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	ROSALIND FRANKLIN UNIVERSITY OF MEDICINE AND SCIENCE	3333 GREEN BAY RD	NORTH CHICAGO	IL	60064	LAKE	USA	Mental Health Research Grants	000	5	12/30/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $390,000 )
2019	2019	ROSALIND FRANKLIN UNIVERSITY OF MEDICINE AND SCIENCE	3333 GREEN BAY RD	NORTH CHICAGO	IL	60064	LAKE	USA	Mental Health Research Grants	000	5	11/20/2018	NON-COMPETING CONTINUATION	$390,000
														Subtotal = $390,000

Issue Date FY: 2018 ( Subtotal = $390,000 )
2018	2018	ROSALIND FRANKLIN UNIVERSITY OF MEDICINE AND SCIENCE	3333 GREEN BAY RD	NORTH CHICAGO	IL	60064	LAKE	USA	Mental Health Research Grants	000	4	11/21/2017	NON-COMPETING CONTINUATION	$351,000
2018	2018	ROSALIND FRANKLIN UNIVERSITY OF MEDICINE AND SCIENCE	3333 GREEN BAY RD	NORTH CHICAGO	IL	60064	LAKE	USA	Mental Health Research Grants	001	4	6/15/2018	NON-COMPETING CONTINUATION	$39,000
														Subtotal = $390,000

Issue Date FY: 2017 ( Subtotal = $390,000 )
2017	2017	ROSALIND FRANKLIN UNIVERSITY OF MEDICINE AND SCIENCE	3333 GREEN BAY RD	NORTH CHICAGO	IL	60064	LAKE	USA	Mental Health Research Grants	001	3	5/29/2017	NON-COMPETING CONTINUATION	$39,000
2017	2017	ROSALIND FRANKLIN UNIVERSITY OF MEDICINE AND SCIENCE	3333 GREEN BAY RD	NORTH CHICAGO	IL	60064	LAKE	USA	Mental Health Research Grants	000	3	11/16/2016	NON-COMPETING CONTINUATION	$351,000
														Subtotal = $390,000

Issue Date FY: 2016 ( Subtotal = $390,000 )
2016	2016	ROSALIND FRANKLIN UNIVERSITY OF MEDICINE & SCIENCE	3333 GREEN BAY ROAD	NORTH CHICAGO	IL	60064	LAKE	USA	Mental Health Research Grants	001	2	3/10/2016	NON-COMPETING CONTINUATION	$39,000
2016	2016	ROSALIND FRANKLIN UNIVERSITY OF MEDICINE & SCIENCE	3333 GREEN BAY ROAD	NORTH CHICAGO	IL	60064	LAKE	USA	Mental Health Research Grants	000	2	11/10/2015	NON-COMPETING CONTINUATION	$351,000
														Subtotal = $390,000

Issue Date FY: 2015 ( Subtotal = $390,000 )
2015	2015	ROSALIND FRANKLIN UNIVERSITY OF MEDICINE & SCIENCE	3333 GREEN BAY ROAD	NORTH CHICAGO	IL	60064	LAKE	USA	Mental Health Research Grants	001	1	6/16/2015	NEW	$3,750
2015	2015	ROSALIND FRANKLIN UNIVERSITY OF MEDICINE & SCIENCE	3333 GREEN BAY ROAD	NORTH CHICAGO	IL	60064	LAKE	USA	Mental Health Research Grants	000	1	11/24/2014	NEW	$386,250
														Subtotal = $390,000

Grand Total All Awards = $1,923,151

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Amygdala and Pain-Associated Mood Disorders

Award Number: R01MH105528

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2014

PERIOD OF PERFORMANCE END DATE: 11/30/2021

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