Files and links (1)
Published, Version of Record (VoR)Open Access via Drexel Libraries Read and Publish Program 2024CC BY-NC-ND V4.0, Open
Journal article
Inflammatory pain resolution by mouse serum-derived small extracellular vesicles
Brain, behavior, and immunity, v 123, pp 422-441
05 Oct 2024
PMID: 39349284
Featured in Collection : Research Supported by Drexel Libraries' OA Programs
Abstract
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.
Metrics
Details
- Title
- Inflammatory pain resolution by mouse serum-derived small extracellular vesicles
- Creators
- Zhucheng Lin - Department of Pharmacology & Physiology, Drexel University College of Medicine, 245 North 15th Street, Mail Stop 488, Room 8223, Philadelphia, PA 19102, USAXuan Luo - Drexel UniversityJason R Wickman - Drexel University, Pharmacology and PhysiologyDeepa Reddy - Drexel UniversityJason T DaCunza - Drexel UniversityRicha Pande - Drexel University, Pharmacology and PhysiologyYuzhen Tian - Drexel University, Pharmacology and PhysiologyEzgi E Kasimoglu - Drexel UniversityVivian Triana - Nanostics Inc., Edmonton, Alberta T5J 4P6, CanadaJingyun Lee - Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USACristina M Furdui - Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USADesmond Pink - Nanostics Inc., Edmonton, Alberta T5J 4P6, CanadaAhmet Sacan - Drexel University, School of Biomedical Engineering, Science, and Health SystemsSeena K Ajit (Corresponding Author) - Drexel University, Pharmacology and Physiology
- Publication Details
- Brain, behavior, and immunity, v 123, pp 422-441
- Publisher
- Elsevier
- Number of pages
- 20
- Grants
- Grant note
- We would like to acknowledge the support provided by the Proteomics and Metabolomics Shared Resource of the Wake Forest School of Medicine and Wake Forest Baptist Comprehensive Cancer Center (NIH/NCI P30 CA12197).
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology; School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:001333235100001
- Scopus ID
- 2-s2.0-85205562911
- Other Identifier
- 991021903507104721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology
- Neurosciences
- Psychiatry