Thursday, October 23, 2025 10/23/2025

Small extracellular vesicles mediated signaling and pain

Award Number: R01NS129191
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: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Small extracellular vesicles mediated signaling and pain - Abstract Chronic pain is the most prevalent, disabling, and expensive public health condition in the United States. The goal of this project is to elucidate how to harness body’s own analgesic mechanisms to provide pain relief. We propose to investigate 30-150 nm small extracellular vesicles (sEVs) that transport mRNAs, miRNAs, proteins, and lipid mediators to recipient cells via circulation. Uptake of sEVs induce gene expression changes in recipient cells and thus, sEVs play an important role in intercellular communication. We observed that sEVs from RAW 264.7 macrophage cells show therapeutic and prophylactic efficacy in a complete Freud adjuvant (CFA) mouse model of inflammatory pain. Our preliminary studies show that mouse serum derived sEVs also conferred prophylaxis when injected intrathecally in naïve recipient mice that, two weeks later, received a hind paw injection of CFA. Thus, mice that received sEVs can remember this stimulation for at least 2 weeks and show an attenuated response to CFA. How this long-term memory develop is unknown. Though chronic pain is prevalent, an immunization strategy has not yet been tested and our studies will provide the rationale and mechanistic basis for such a strategy. Here we propose to test the hypothesis that monocyte/macrophage-derived sEV subsets in serum are necessary and sufficient to attenuate inflammatory pain hypersensitivity and confer prophylaxis. We will also investigate if monocyte/macrophage sEVs recruit, or promote anti- inflammatory phenotype switching of immune cells in dorsal root ganglion and spinal cord by quantitative immunophenotyping in situ, before and after CFA treatment. Recent studies show that microglia, the resident macrophages of the central nervous system can enhance or suppress responses to a delayed secondary insult through epigenetic modifications. We hypothesize that monocyte/macrophage-derived sEVs impart epigenetic immune memory in spinal microglia of recipient mice, granting the capacity to attenuate pain from a future insult and contribute to the prophylactic effect of sEVs. The studies proposed will elucidate the role of sEVs in immune regulation and memory.


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 = $382,851 )
2025	2025	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	7/3/2025	NON-COMPETING CONTINUATION	$382,851
														Subtotal = $382,851

Issue Date FY: 2024 ( Subtotal = $393,188 )
2024	2024	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	5/20/2024	NON-COMPETING CONTINUATION	$393,188
														Subtotal = $393,188

Issue Date FY: 2023 ( Subtotal = $425,097 )
2023	2023	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	5/15/2023	NON-COMPETING CONTINUATION	$425,097
														Subtotal = $425,097

Issue Date FY: 2022 ( Subtotal = $425,097 )
2022	2022	DREXEL UNIVERSITY	3141 CHESTNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/17/2022	NEW	$425,097
														Subtotal = $425,097

Grand Total All Awards = $1,626,233

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Small extracellular vesicles mediated signaling and pain

Award Number: R01NS129191

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: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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