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Regulation of SCI-induced pain by macrophages and exercise

Award Number: R01NS097880
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/18/2017
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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Regulation of SCI-induced pain by macrophages and exercise - PROJECT SUMMARY Spinal cord injury (SCI) impairs sensory transmission and leads to chronic, debilitating neuropathic pain. Chronic pain afflicts over 100 million Americans and creates an enormous burden on US health care systems, costing over half a trillion dollars annually according to a recent report from the Institute of Medicine. While our understanding of the molecular basis underlying the development of chronic pain has improved, the available therapeutics provide limited relief. While our lab and others have shown that early post-SCI rehab can prevent pain development, early rehab in human SCI may not be possible due to the multisystem, polytraumatic injuries individuals with SCI sustain. Thus, there is a critical need for an adjuvant therapy to aid those individuals who are unable to participate in early rehab. Neuropathic pain is increasingly recognized as a neuroimmune disorder. While macrophages are regarded as key regulators of chronic pain development, it is unclear whether they are acting in an inflammatory or reparative manner. This R01 seeks to better understand how or if the activation state of macrophages influences nociceptive neuron excitability and pain development after SCI. We will utilize an established spinal cord injury model of neuropathic pain development and drive macrophage activation state by post-injury rehab, intrathecal administration of exosomes derived from Raw 264.7 macrophages stimulated in vitro or a phosphodiesterase 4 inhibitor by a polymer nanodelivery system that specifically targets macrophages. This proposal seeks to understand the role of macrophages that infiltrate the dorsal root ganglia and persist there chronically after SCI both in the development and maintenance of 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: 2025 ( Subtotal = $233,500 )
2025	2025	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	8	7/28/2025	NON-COMPETING CONTINUATION	$413,368
2025	2021	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	10/1/2024	NON-COMPETING CONTINUATION	-$179,868
														Subtotal = $233,500

Issue Date FY: 2024 ( Subtotal = $416,494 )
2024	2024	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	7/16/2024	NON-COMPETING CONTINUATION	$416,494
														Subtotal = $416,494

Issue Date FY: 2023 ( Subtotal = $442,615 )
2023	2023	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	6	9/18/2023	COMPETING CONTINUATION	$442,615
2023	2021	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	7/28/2023	NON-COMPETING CONTINUATION	$0
2023	2021	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	9/18/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $442,615

Issue Date FY: 2021 ( Subtotal = $337,979 )
2021	2021	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	8/23/2021	NON-COMPETING CONTINUATION	$337,979
														Subtotal = $337,979

Issue Date FY: 2020 ( Subtotal = $337,979 )
2020	2020	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	7/30/2020	NON-COMPETING CONTINUATION	$337,979
														Subtotal = $337,979

Issue Date FY: 2019 ( Subtotal = $938,534 )
2019	2019	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	6/27/2019	NON-COMPETING CONTINUATION	$337,742
2019	2019	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	000	2	4/4/2019	SUPPLEMENT FOR EXPANSION	$600,792
														Subtotal = $938,534

Issue Date FY: 2018 ( Subtotal = $334,618 )
2018	2018	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	6/21/2018	NON-COMPETING CONTINUATION	$334,618
														Subtotal = $334,618

Issue Date FY: 2017 ( Subtotal = $320,726 )
2017	2017	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/21/2017	NEW	$320,726
														Subtotal = $320,726

Grand Total All Awards = $3,362,445

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Regulation of SCI-induced pain by macrophages and exercise

Award Number: R01NS097880

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/18/2017

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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