Preprint
Inflammatory pain resolution by mouse serum-derived small extracellular vesicles
bioRxiv : the preprint server for biology
18 Feb 2024
PMID: 38405813
Abstract
Chronic pain is a significant public health issue. Current treatments have limited efficacy and significant side effects, warranting research on alternative strategies for pain management. One approach involves using small extracellular vesicles (sEVs) to transport beneficial biomolecular cargo to aid pain resolution. Exosomes are 30-150 nm sEVs that can carry RNAs, proteins, and lipid mediators to recipient cells via circulation. Exosomes can be beneficial or harmful depending on their source and contents. 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 donor mice were injected intrathecally into naïve recipient mice. Basal mechanical thresholds transiently increased in recipient mice. This effect was mediated by opioid signaling as this outcome was blocked by naltrexone. Mass Spectrometry of sEVs detected endogenous opioid peptide leu-enkephalin. A single prophylactic intrathecal injection of sEVs two weeks prior to induction of the pain model in recipient mice delayed mechanical allodynia in SNI model mice and accelerated recovery from inflammatory pain after complete Freund's adjuvant (CFA) injection. ChipCytometry of spinal cord and dorsal root ganglion (DRG) from sEV treated mice showed that prophylactic sEV treatment reduced the number of natural killer (NK) and NKT cells in spinal cord and increased CD206+ anti-inflammatory macrophages in (DRG) after CFA injection. Further characterization of sEVs showed the presence of immune markers suggesting that sEVs can exert immunomodulatory effects in recipient mice to promote the resolution of inflammatory pain. Collectively, these studies demonstrate multiple mechanisms by which sEVs can attenuate pain.
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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, Philadelphia, PA 19102, USAXuan Luo - Drexel UniversityJason R Wickman - Drexel University, Pharmacology and PhysiologyDeepa Reddy - Drexel UniversityRicha Pande - Drexel University, Pharmacology and PhysiologyYuzhen Tian - Drexel University, Pharmacology and PhysiologyVivian 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 - Drexel University, Pharmacology and Physiology
- Publication Details
- bioRxiv : the preprint server for biology
- Publisher
- United States
- Grant note
- R01 NS102836 / NINDS NIH HHS P30 CA012197 / NCI NIH HHS R01 NS129191 / NINDS NIH HHS RF1 NS130481 / NINDS NIH HHS
- Resource Type
- Preprint
- Language
- English
- Academic Unit
- Pharmacology and Physiology; School of Biomedical Engineering, Science, and Health Systems
- Other Identifier
- 991021855250204721