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Macrophage Derived Small Extracellular Vesicles As A Therapeutic For Postoperative Pain And Inflammation
Abstract   Open access   Peer reviewed

Macrophage Derived Small Extracellular Vesicles As A Therapeutic For Postoperative Pain And Inflammation

Deepa Reddy, Jason Wickman, Yuzhen Tian and Seena Ajit
The journal of pain, v 24(4), pp 15-15
Apr 2023
DOI: https://doi.org/10.1016/j.jpain.2023.02.083
url
https://doi.org/10.1016/j.jpain.2023.02.083View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open

Abstract

Surgeries induce post-operative pain that must be alleviated effectively to reduce suffering, and to promote healing and recovery. Depending on the surgery and the specific conditions, post-operative pain is not effectively managed in >80% of the patients in US. Traditional opioids, such as morphine, remain the standard of care for perioperative pain regulation. Limitations of opioid use include a narrow therapeutic window, undesirable adverse events, and toxicity. Better treatment strategies are needed during and immediately after surgery to prevent the progression of acute pain to long term persistent pain. Small extracellular vesicles (sEVs), including exosomes, mediate intercellular communication by carrying biomolecular cargo to recipient cells. Our previous studies have shown that sEVs isolated from macrophage derived RAW 264.7 cells attenuate pain and inflammation in a mouse model of inflammatory pain. We hypothesize that macrophage-derived sEVs can attenuate post-operative pain therapeutically (administered immediately after surgery) or prophylactically (administered 2 weeks prior to surgery), decreasing the dose and duration of analgesic needed for pain relief. We generated and validated the model and our preliminary data reveal sEVs given after surgery results in faster attenuation of hypersensitivity compared to control. Future studies will determine the synergistic effect of therapeutic and prophylactic sEVs, to assess whether sEVs can a) lower the efficacious dose of commonly prescribed analgesic drugs or b) increase the duration of pain relief in a post-operative pain model. Studies are ongoing to elucidate the mechanisms underlying efficacy of sEVs, including immune cell trafficking in paw tissue.

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