Therapeutic and prophylactic effects of macrophage-derived small extracellular vesicles in the attenuation of inflammatory pain.
Journal
Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
03
09
2020
revised:
28
01
2021
accepted:
06
02
2021
pubmed:
20
2
2021
medline:
29
5
2021
entrez:
19
2
2021
Statut:
ppublish
Résumé
Small extracellular vesicles (sEVs) derived from antigen-presenting cells such as macrophages can induce therapeutically relevant immune responses. Anti-inflammatory 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.
Identifiants
pubmed: 33607232
pii: S0889-1591(21)00047-7
doi: 10.1016/j.bbi.2021.02.005
pmc: PMC8058272
mid: NIHMS1674552
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
210-224Subventions
Organisme : NINDS NIH HHS
ID : R01 NS102836
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
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