Sunday, May 11, 2025 5/11/2025

Study of Activity-Dependent Sympathetic Sprouting

Award Number: R01NS045594
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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Study of Activity-Dependent Sympathetic Sprouting - The role of the sympathetic nervous system (SNS) in regulating pain and inflammation has been well- established in animal models. In the clinic, sympathetic blockade is often used for managing neuropathic pain such as CRPS. The efficacy was evidenced by a recent clinical study showing dramatic and promising results using a catheter approach to provide longer lasting sympathetic blockade than is achieved by injection, in patients with intractable neuropathic pain. Mechanisms underlying SNS-mediated pain revealed by our group and our collaborators in the past 20 years include: activity associated SNS sprouting; generation of spontaneous activity; immune and inflammatory response; clustered firing of sensory neurons. We reported recently that persistent neuropathic pain is driven by active nerve regeneration. Our preliminary data also showed that sympathetic-mediated macrophage activation may be important in nerve regeneration as well as neuronal survival after nerve injury. Most interestingly, we found sympathetic-mediated immune/inflammatory responses, nerve regeneration, and pain behaviors could be reversed when the adjacent sciatic lymph node (LN) was removed, suggesting SNS-lymph node interactions may be critical for the development and possibly management of neuropathic pain. We hypothesize that sympathetic sprouting and its interactions with sensory neurons after nerve injury are neuroprotective and that sympathetic activation promotes cell survival but enhances pain due to increased nerve/axonal regeneration. We further hypothesize that SNS mediates immune responses, nerve regeneration, and cell survival by manipulation of macrophage activation, and, at least, partially, by interactions with adjacent lymph nodes. The hypothesis will be tested in three specific aims (SA): SA1: To determine whether sympathetic innervation is neuroprotective after peripheral nerve injury. SA2: To examine the relationships between cell death, regeneration, and macrophage subtypes in mouse models of neuropathic pain. SA3: To determine the role and function of adjacent lymph nodes (LN) in sympathetic regulation of immune response, nerve regeneration and cell survival. Our hypothesis proposes some novel concepts and represents a new direction for the study of sympathetic influences on pain and inflammation. The proposed studies will investigate and characterize, for the first-time, the sympathetic influences on neuronal survival, axonal regeneration at the level of sensory ganglia, and its interactions with lymph nodes in neuropathic pain conditions, which have high incidence, cost, and morbidity and for which effective treatments are often unavailable or unsatisfactory.


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 = $519,198 )
2024	2024	CINCINNATI UNIV OF	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	19	6/17/2024	NON-COMPETING CONTINUATION	$519,198
														Subtotal = $519,198

Issue Date FY: 2023 ( Subtotal = $535,255 )
2023	2023	UNIVERSITY OF CINCINNATI	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	18	7/11/2023	NON-COMPETING CONTINUATION	$535,255
														Subtotal = $535,255

Issue Date FY: 2022 ( Subtotal = $535,255 )
2022	2022	UNIVERSITY OF CINCINNATI	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	17	8/24/2022	NON-COMPETING CONTINUATION	$535,255
2022	2021	UNIVERSITY OF CINCINNATI	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	16	1/12/2022	COMPETING CONTINUATION	$131,383
2022	2020	UNIVERSITY OF CINCINNATI	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	1/12/2022	NON-COMPETING CONTINUATION	-$131,383
														Subtotal = $535,255

Issue Date FY: 2021 ( Subtotal = $550,755 )
2021	2021	UNIVERSITY OF CINCINNATI	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	16	7/6/2021	COMPETING CONTINUATION	$550,755
2021	2020	UNIVERSITY OF CINCINNATI	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	7/5/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $550,755

Issue Date FY: 2020 ( Subtotal = $787,379 )
2020	2020	UNIVERSITY OF CINCINNATI	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	2/13/2020	NON-COMPETING CONTINUATION	$787,379
														Subtotal = $787,379

Issue Date FY: 2019 ( Subtotal = $786,634 )
2019	2019	UNIVERSITY OF CINCINNATI	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Drug Use and Addiction Research Programs	001	14	8/30/2019	SUPPLEMENT FOR EXPANSION	$401,250
2019	2019	UNIVERSITY OF CINCINNATI	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	1/15/2019	NON-COMPETING CONTINUATION	$385,384
														Subtotal = $786,634

Issue Date FY: 2018 ( Subtotal = $389,483 )
2018	2018	UNIVERSITY OF CINCINNATI	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	13	6/8/2018	NON-COMPETING CONTINUATION	$38,946
2018	2018	UNIVERSITY OF CINCINNATI	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	1/16/2018	NON-COMPETING CONTINUATION	$350,537
														Subtotal = $389,483

Issue Date FY: 2017 ( Subtotal = $388,764 )
2017	2017	UNIVERSITY OF CINCINNATI	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	1/27/2017	NON-COMPETING CONTINUATION	$349,889
2017	2017	UNIVERSITY OF CINCINNATI	2600 CLIFTON AVE	CINCINNATI	OH	45220	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	12	5/31/2017	NON-COMPETING CONTINUATION	$38,875
														Subtotal = $388,764

Issue Date FY: 2016 ( Subtotal = $402,828 )
2016	2016	UNIVERSITY OF CINCINNATI	PO BOX 210225	CINCINNATI	OH	45221	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	11	1/25/2016	COMPETING CONTINUATION	$402,828
2016	2014	UNIVERSITY OF CINCINNATI	PO BOX 210225	CINCINNATI	OH	452210225	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	1/20/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $402,828

Issue Date FY: 2014 ( Subtotal = $333,203 )
2014	2014	UNIVERSITY OF CINCINNATI	PO BOX 210225	CINCINNATI	OH	45221	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	4/10/2014	NON-COMPETING CONTINUATION	$333,203
														Subtotal = $333,203

Issue Date FY: 2013 ( Subtotal = $324,789 )
2013	2013	UNIVERSITY OF CINCINNATI	PO BOX 210225	CINCINNATI	OH	45221	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	4/25/2013	NON-COMPETING CONTINUATION	$302,913
2013	2013	UNIVERSITY OF CINCINNATI	PO BOX 210225	CINCINNATI	OH	45221	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	9	5/23/2013	NON-COMPETING CONTINUATION	$21,876
														Subtotal = $324,789

Issue Date FY: 2012 ( Subtotal = $336,569 )
2012	2012	UNIVERSITY OF CINCINNATI	PO BOX 210225	CINCINNATI	OH	45221	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	3/14/2012	NON-COMPETING CONTINUATION	$336,569
														Subtotal = $336,569

Issue Date FY: 2011 ( Subtotal = $336,569 )
2011	2011	UNIVERSITY OF CINCINNATI	PO BOX 210225	CINCINNATI	OH	45221	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	3/16/2011	NON-COMPETING CONTINUATION	$309,094
2011	2011	UNIVERSITY OF CINCINNATI	PO BOX 210225	CINCINNATI	OH	45221	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	7	6/22/2011	NON-COMPETING CONTINUATION	$27,475
														Subtotal = $336,569

Issue Date FY: 2010 ( Subtotal = $410,969 )
2010	2010	UNIVERSITY OF CINCINNATI	PO BOX 210225	CINCINNATI	OH	45221	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	4/21/2010	COMPETING CONTINUATION	$330,969
2010	2005	UNIVERSITY OF CINCINNATI	PO BOX 210225	CINCINNATI	OH	45221	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	6/29/2010	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$80,000
														Subtotal = $410,969

Issue Date FY: 2008 ( Subtotal = $269,260 )
2008	2008	UNIVERSITY OF CINCINNATI	PO BOX 210225	CINCINNATI	OH	45221	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	3/10/2008	NON-COMPETING CONTINUATION	$269,260
														Subtotal = $269,260

Issue Date FY: 2007 ( Subtotal = $269,260 )
2007	2007	UNIVERSITY OF CINCINNATI	PO BOX 210225	CINCINNATI	OH	45221	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	4/26/2007	NON-COMPETING CONTINUATION	$269,260
														Subtotal = $269,260

Issue Date FY: 2006 ( Subtotal = $277,302 )
2006	2006	UNIVERSITY OF CINCINNATI	PO BOX 210225	CINCINNATI	OH	45221	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	4/19/2006	NON-COMPETING CONTINUATION	$277,302
														Subtotal = $277,302

Issue Date FY: 2005 ( Subtotal = $283,975 )
2005	2005	UNIVERSITY OF CINCINNATI	PO BOX 210225	CINCINNATI	OH	45221	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	9/1/2005	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$283,975
														Subtotal = $283,975

Issue Date FY: 2004 ( Subtotal = $285,038 )
2004	2004	UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES	4301 W MARKHAM ST, M S 545	LITTLE ROCK	AR	72205	PULASKI	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/4/2004	NEW	$285,038
														Subtotal = $285,038

Grand Total All Awards = $8,022,485

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Study of Activity-Dependent Sympathetic Sprouting

Award Number: R01NS045594

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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