Abstract
Immune Regulation By Small Extracellular Vesicles In Attenuating Inflammatory Pain
The journal of pain, v 24(4), pp 9-9
Apr 2023
Abstract
Chronic pain affects millions in the United States. Pain is not generated by a hardwired system, but rather by highly plastic circuits and molecules. Such molecules can be small extracellular vesicles (sEVs) released by cells that transport RNAs, proteins, and lipids. Uptake of sEV cargo by recipient cells can alter gene expression, and this process can serve as a novel mechanism of cellular communication. We showed that sEVs from RAW 264.7 macrophages are immunomodulatory, and prophylactic injection of sEVs two weeks prior, attenuated inflammatory pain induced by complete Freund's adjuvant (CFA). How this long-term memory develops and how sEVs regulate immune responses are unknown. Recent studies show that microglia that were primed with inflammatory stimuli can enhance or suppress responses to a delayed secondary insult via epigenetic modifications. We hypothesize that prophylactic macrophage-derived sEVs, when administered intrathecally, confer pain resolution by reprogramming epigenetic immune memory in spinal microglia and by promoting anti-inflammatory immune responses in recipient mice. Our preliminary data demonstrate that spinal microglia from CFA mice that previously received sEVs have lower pro-inflammatory cytokine mRNA expression. To study immune cell dynamics in spinal cord of CFA recipient mice, a high-plex spatial assay, ChipCytometry, was used. We observed a decrease in natural killer (NK) cells in spinal cord in CFA mice prophylactically treated with sEVs compared to control mice. Studies are ongoing to investigate if this sEV-conferred prophylaxis is mediated by epigenetic alterations in spinal microglia, and how sEVs regulate immune cells in spinal cord to induce pain resolution. R01 NS102836, R01 NS129191, RF1 NS130481.
Metrics
24 Record Views
Details
- Title
- Immune Regulation By Small Extracellular Vesicles In Attenuating Inflammatory Pain
- Creators
- Xuan Luo - Drexel UniversityAhmet Sacan - Drexel UniversitySeena Ajit - Drexel University
- Publication Details
- The journal of pain, v 24(4), pp 9-9
- Publisher
- Elsevier
- Number of pages
- 1
- Resource Type
- Abstract
- Language
- English
- Academic Unit
- College of Medicine; Pharmacology and Physiology; School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Other Identifier
- 991020262643704721