Macrophage-derived small extracellular vesicles as a therapeutic for postoperative pain and inflammation 9004

Abstract Description Surgeries induce post-operative pain that must be alleviated to limit suffering and promote recovery. Post-operative pain is not effectively managed in > 80% of patients in the US. Opioids are the standard of care for perioperative pain, but dosing is limited due to adverse effects and abuse potential. Small extracellular vesicles (sEVs), including exosomes, mediate intercellular communication by carrying biomolecular cargo to recipient cells. We have previously shown that sEVs isolated from macrophage-derived RAW 264.7 cells attenuate pain in mouse models of inflammatory pain. Here we hypothesize that macrophage-derived sEVs can attenuate post-operative pain. We observed that intraplantar sEVs given three hours before plantar incisional surgery significantly attenuate pain as compared to control mice. To probe the mechanistic underpinnings, flow cytometry studies on paw and dorsal root ganglia (DRG) tissue were performed on post-operative days one and three. We observed an increase and decrease in pro-resolution (CD206+, CD163+) and pro-inflammatory (CD86+, MHCII+) macrophage phenotypes, respectively, in sEV treated mice compared to controls. Additionally, there was an increase in activated neutrophils (CD11bhi, CD18+) in sEV treated mice. Studies are ongoing to determine whether these changes in immune cell phenotypes are necessary for sEV action using depletion and pharmacological inhibition of specific macrophage and neutrophil populations. Funding Sources NIH NINDS R01NS102836, R01NS129191 and RF1NS130481 to Seena Ajit. ? Drexel Univeristy College of Medicine’s Dean’s Fellowship to Deepa Reddy. Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)