Inflammatory pain resolution by mouse serum-derived small extracellular vesicles.

Autor: Lin Z; Department of Pharmacology & Physiology, Drexel University College of Medicine, 245 North 15th Street, Mail Stop 488, Room 8223, Philadelphia, PA 19102, USA., Luo X; Department of Pharmacology & Physiology, Drexel University College of Medicine, 245 North 15th Street, Mail Stop 488, Room 8223, Philadelphia, PA 19102, USA., Wickman JR; Department of Pharmacology & Physiology, Drexel University College of Medicine, 245 North 15th Street, Mail Stop 488, Room 8223, Philadelphia, PA 19102, USA., Reddy D; Department of Pharmacology & Physiology, Drexel University College of Medicine, 245 North 15th Street, Mail Stop 488, Room 8223, Philadelphia, PA 19102, USA., DaCunza JT; Department of Pharmacology & Physiology, Drexel University College of Medicine, 245 North 15th Street, Mail Stop 488, Room 8223, Philadelphia, PA 19102, USA., Pande R; Department of Pharmacology & Physiology, Drexel University College of Medicine, 245 North 15th Street, Mail Stop 488, Room 8223, Philadelphia, PA 19102, USA., Tian Y; Department of Pharmacology & Physiology, Drexel University College of Medicine, 245 North 15th Street, Mail Stop 488, Room 8223, Philadelphia, PA 19102, USA., Kasimoglu EE; Department of Pharmacology & Physiology, Drexel University College of Medicine, 245 North 15th Street, Mail Stop 488, Room 8223, Philadelphia, PA 19102, USA., Triana V; Nanostics Inc., Edmonton, Alberta T5J 4P6, Canada., Lee J; Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA., Furdui CM; Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA., Pink D; Nanostics Inc., Edmonton, Alberta T5J 4P6, Canada., Sacan A; School of Biomedical Engineering, Science & Health Systems, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104, USA., Ajit SK; Department of Pharmacology & Physiology, Drexel University College of Medicine, 245 North 15th Street, Mail Stop 488, Room 8223, Philadelphia, PA 19102, USA. Electronic address: ska52@drexel.edu.
Jazyk: angličtina
Zdroj: Brain, behavior, and immunity [Brain Behav Immun] 2024 Sep 29; Vol. 123, pp. 422-441. Date of Electronic Publication: 2024 Sep 29.
DOI: 10.1016/j.bbi.2024.09.032
Abstrakt: Current treatments for chronic pain have limited efficacy and significant side effects, warranting research on alternative strategies for pain management. One approach involves using small extracellular vesicles (sEVs), or exosomes, to transport beneficial biomolecular cargo to aid pain resolution. Exosomes are 30-150 nm sEVs that can be beneficial or harmful depending on their source and cargo composition. We report a comprehensive multi-modal analysis of different aspects of sEV characterization, miRNAs, and protein markers across sEV sources. To investigate the short- and long-term effects of mouse serum-derived sEVs in pain modulation, sEVs from naïve control or spared nerve injury (SNI) model male donor mice were injected intrathecally into naïve male recipient mice. These sEVs transiently increased basal mechanical thresholds, an effect mediated by opioid signaling as this outcome was blocked by naltrexone. Mass spectrometry of sEVs detected endogenous opioid peptide leu-enkephalin. sEVs from naïve female mice have higher levels of leu-enkephalin compared to male, matching the analgesic onset of leu-enkephalin in male recipient mice. In investigating the long-term effect of sEVs, we observed that a single prophylactic intrathecal injection of sEVs two weeks prior to induction of the pain model in recipient mice accelerated recovery from inflammatory pain after complete Freund's adjuvant (CFA) injection. Our exploratory studies examining immune cell populations in spinal cord and dorsal root ganglion using ChipCytometry suggested alterations in immune cell populations 14 days post-CFA. Flow cytometry confirmed increases in CD206 + macrophages in the spinal cord in sEV-treated mice. Collectively, these studies demonstrate multiple mechanisms by which sEVs can attenuate pain.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: