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Amygdala pain mechanisms

Award Number: R01NS038261
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary Chronic pain, a complex multidimensional disorder, remains a major health care issue and a therapeutic challenge. The development of new and improved therapeutic strategies requires the full understanding of mechanisms of chronic pain at all levels of the neuraxis and for all cell types, including non-neuronal elements. Neuroimmune signaling has emerged as a peripheral and spinal pain mechanism, but little is known about the role, regulation and therapeutic potential of molecular crosstalk between neuronal and glial cell types in the brain in the context of pain. To address this important knowledge gap we will build on our NIH-funded work (since 1999) that impacted the field by identifying neuroplasticity in the amygdala, a brain center for emotions, as a critical mechanism for emotional-affective aspects of pain and pain modulation. The proposed project will test the novel hypothesis that chronification of amygdala plasticity and neuropathic pain behaviors depends on a cascade of neuroimmune signaling that can be targeted to mitigate neuropathic pain. Specifically, enhanced synaptic drive of certain amygdala neuron types at the acute pain stage activates different types of glia, and glia-derived factors generate hyperexcitability in distinct amygdala neuron types at the chronic stage to maintain neuropathic pain. A comprehensive multidisciplinary approach will be used that integrates state-of-the-art transcriptomics, bioinformatics, behavioral assays, brain slice electrophysiology, pharmacology, chemogenetics, optogenetics, viral vector strategies, immunohistochemistry and molecular biology for the analysis of neuroimmune interactions within and between different types of neuronal and glial cells in the amygdala output region (central nucleus, CeA) in the well-established spinal nerve ligation (SNL) rat model of neuropathic pain. Male and female rats will be studied. A transgenic Crh-Cre rat model will be used to study the CeA corticotropin releasing factor (CRF) system, an important player in amygdala plasticity, and its role in neuroimmune signaling. Aim 1 will use a combination of cell-specific bulk and single-cell RNA sequencing (scRNA-Seq) to identify individual genes, molecular pathways and functional cellular states associated with pain chronification. A novel computational scRNA-Seq- based interactome analysis will determine neuron-glia interactions at the acute and chronic stages of neuropathic pain and identify drug-targetable molecular factors. Aim 2 will determine the behavioral significance of neuron-glia-neuron signaling in the CeA at different stages of neuropathic pain, using chemogenetic activation and inhibition of different cell types and pharmacological (or viral based) tools to modulate molecular factors. Sensory thresholds, emotional responses, non-evoked ongoing pain, and anxiety- and depression-like behaviors will be measured. Aim 3 will determine electrophysiological mechanisms of neuron-glia-neuron signaling in the CeA at different stages of neuropathic pain, using patch-clamp recordings of different cell types in brain slices and chemogenetic and pharmacological (or viral based) manipulations. Successful completion of these conceptually innovative studies will significantly advance our knowledge of neuro-immune signaling in brain plasticity and in the transition from acute to chronic pain and provide novel targets to mitigate chronic neuropathic 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: 2024 ( Subtotal = $496,430 )
2024	2024	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH STREET	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	25	12/19/2023	NON-COMPETING CONTINUATION	$496,430
														Subtotal = $496,430

Issue Date FY: 2023 ( Subtotal = $551,588 )
2023	2023	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH STREET	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	24	12/22/2022	NON-COMPETING CONTINUATION	$496,430
2023	2023	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH STREET	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	24	2/1/2023	NON-COMPETING CONTINUATION	$55,158
														Subtotal = $551,588

Issue Date FY: 2022 ( Subtotal = $551,588 )
2022	2022	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH STREET	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	23	6/8/2022	COMPETING CONTINUATION	$128,474
2022	2022	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH STREET	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	23	12/15/2021	COMPETING CONTINUATION	$551,588
2022	2021	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH STREET	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	22	6/8/2022	NON-COMPETING CONTINUATION	-$128,474
2022	2021	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH STREET	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	22	12/13/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $551,588

Issue Date FY: 2021 ( Subtotal = $334,688 )
2021	2021	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH STREET	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	22	12/18/2020	NON-COMPETING CONTINUATION	$301,219
2021	2021	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH STREET	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	22	1/25/2021	NON-COMPETING CONTINUATION	$33,469
														Subtotal = $334,688

Issue Date FY: 2020 ( Subtotal = $334,688 )
2020	2020	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH STREET	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	21	2/20/2020	NON-COMPETING CONTINUATION	$33,469
2020	2020	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH STREET	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	21	11/27/2019	NON-COMPETING CONTINUATION	$301,219
														Subtotal = $334,688

Issue Date FY: 2019 ( Subtotal = $334,688 )
2019	2019	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH ST	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	20	11/30/2018	NON-COMPETING CONTINUATION	$334,688
														Subtotal = $334,688

Issue Date FY: 2018 ( Subtotal = $334,688 )
2018	2018	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH ST MS 6271	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	19	11/30/2017	NON-COMPETING CONTINUATION	$301,219
2018	2018	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH ST	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	19	4/26/2018	NON-COMPETING CONTINUATION	$33,469
														Subtotal = $334,688

Issue Date FY: 2017 ( Subtotal = $334,688 )
2017	2017	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH ST MS 6271	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	18	2/24/2017	COMPETING CONTINUATION	$166,984
2017	2017	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH ST MS 6271	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	18	11/7/2016	COMPETING CONTINUATION	$334,688
2017	2015	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH ST MS 6271	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	11/3/2016	NON-COMPETING CONTINUATION	$0
2017	2015	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH ST MS 6271	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	17	2/24/2017	NON-COMPETING CONTINUATION	-$166,984
														Subtotal = $334,688

Issue Date FY: 2015 ( Subtotal = $330,313 )
2015	2015	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH STREET	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	3/12/2015	NON-COMPETING CONTINUATION	$330,313
														Subtotal = $330,313

Issue Date FY: 2014 ( Subtotal = $331,341 )
2014	2014	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	15	7/16/2014	NON-COMPETING CONTINUATION	-$194,058
2014	2014	TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER	3601 4TH STREET	LUBBOCK	TX	79430	LUBBOCK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	16	7/17/2014	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$194,058
2014	2014	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	3/26/2014	NON-COMPETING CONTINUATION	$331,341
														Subtotal = $331,341

Issue Date FY: 2013 ( Subtotal = $322,974 )
2013	2013	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	14	5/24/2013	NON-COMPETING CONTINUATION	$21,755
2013	2013	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	4/18/2013	NON-COMPETING CONTINUATION	$301,219
														Subtotal = $322,974

Issue Date FY: 2012 ( Subtotal = $334,688 )
2012	2012	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	13	6/12/2012	COMPETING CONTINUATION	$334,688
2012	2011	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	6/8/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $334,688

Issue Date FY: 2011 ( Subtotal = $291,336 )
2011	2011	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	2/14/2011	NON-COMPETING CONTINUATION	$267,554
2011	2011	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	12	6/7/2011	NON-COMPETING CONTINUATION	$23,782
														Subtotal = $291,336

Issue Date FY: 2010 ( Subtotal = $294,308 )
2010	2010	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	1/22/2010	NON-COMPETING CONTINUATION	$294,308
														Subtotal = $294,308

Issue Date FY: 2009 ( Subtotal = $335,081 )
2009	2009	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	1/26/2009	NON-COMPETING CONTINUATION	$267,552
2009	2009	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	10	4/8/2009	SUPPLEMENT FOR EXPANSION	$37,800
2009	2009	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	10	4/6/2009	NON-COMPETING CONTINUATION	$29,729
														Subtotal = $335,081

Issue Date FY: 2008 ( Subtotal = $297,281 )
2008	2008	UNIVERSITY OF TEXAS, MEDICAL BRANCH AT GALVESTON	1000 STRAND	GALVESTON	TX	77550	GALVESTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	2/8/2008	COMPETING CONTINUATION	$297,281
														Subtotal = $297,281

Issue Date FY: 2007 ( Subtotal = $331,093 ) (Continued on the next page)
Grand Total All Awards = $7,841,379

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Amygdala pain mechanisms

Award Number: R01NS038261

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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