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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Therapeutic and prophylactic effects of macrophage-derived small extracellular vesicles in the attenuation of inflammatory pain
Brain, behavior, and immunity, v 94, pp 210-224
01 May 2021
PMID: 33607232
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Small extracellular vesicles (sEVs) derived from antigen-presenting cells such as macrophages can induce therapeutically relevant immune responses. Antiinflammatory miRNAs are elevated in sEVs secreted by RAW 264.7 mouse macrophages after lipopolysaccharide (LPS) stimulation. We observed uptake of these sEVs by primary mouse cortical neurons, microglia and astrocytes followed by downregulation of proinflammatory miRNA target genes in recipient cells. Pre-treating primary microglia with these sEVs decreased pro-inflammatory gene expression. A single intrathecal injection of sEVs derived from LPS stimulated RAW 264.7 cells attenuated mechanical hyperalgesia in the complete Freund?s adjuvant (CFA) mouse model of inflammatory pain and formalin induced acute pain. Importantly, sEVs did not alter the normal pain threshold in control mice. RNA sequencing of dorsal horn of the spinal cord showed sEVs-induced modulation of immune regulatory pathways. Further, a single prophylactic intrathecal injection of sEVs two weeks prior, attenuated CFA-induced pain hypersensitivity and was ineffective in formalin model. This indicates that prophylactic sEVs administration can be beneficial in attenuating chronic pain without impacting responses to the protective physiological and acute inflammatory pain. Prophylactic administration of sEVs could form the basis for a safe and novel vaccine-like therapy for chronic pain or as an adjuvant, potentially reducing the dose of drugs needed for pain relief.
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Details
- Title
- Therapeutic and prophylactic effects of macrophage-derived small extracellular vesicles in the attenuation of inflammatory pain
- Creators
- Renee Jean-Toussaint - Drexel UniversityZhucheng Lin - Drexel UniversityYuzhen Tian - Drexel UniversityRicha Gupta - Drexel UniversityRicha Pande - Drexel UniversityXuan Luo - Drexel UniversityHuijuan Hu - Rutgers, The State University of New JerseyAhmet Sacan - Drexel UniversitySeena K. Ajit - Drexel University
- Publication Details
- Brain, behavior, and immunity, v 94, pp 210-224
- Publisher
- Elsevier
- Number of pages
- 15
- Grant note
- R01NS102836 / NIH NINDS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology; School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000640700000006
- Scopus ID
- 2-s2.0-85101542307
- Other Identifier
- 991019167437104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology
- Neurosciences
- Psychiatry