Therapeutic and prophylactic effects of macrophage-derived small extracellular vesicles in the attenuation of inflammatory pain
| Autor: | Richa Pande, Ahmet Sacan, Yuzhen Tian, Huijuan Hu, Xuan Luo, Renee Jean-Toussaint, Richa Gupta, Zhucheng Lin, Seena K. Ajit |
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| Rok vydání: | 2021 |
| Předmět: |
Pain Threshold
0301 basic medicine Lipopolysaccharide viruses Immunology Pain Pharmacology Article Proinflammatory cytokine Extracellular Vesicles Mice 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound 0302 clinical medicine Immune system Downregulation and upregulation Threshold of pain medicine Animals Macrophage Inflammation Microglia Endocrine and Autonomic Systems business.industry Macrophages Chronic pain virus diseases respiratory system medicine.disease 030104 developmental biology medicine.anatomical_structure Spinal Cord chemistry Hyperalgesia business 030217 neurology & neurosurgery |
| Zdroj: | Brain Behav Immun |
| ISSN: | 0889-1591 |
| DOI: | 10.1016/j.bbi.2021.02.005 |
| Popis: | Small extracellular vesicles (sEVs) derived from antigen-presenting cells such as macrophages can induce therapeutically relevant immune responses. Anti-inflammatory miRNAs are elevated in sEVs secreted by RAW 264.7 mouse macrophages after lipopolysaccharide (LPS) stimulation. We observed uptake of these sEVs by primary mouse cortical neurons, microglia and astrocytes followed by downregulation of proinflammatory miRNA target genes in recipient cells. Pre-treating primary microglia with these sEVs decreased pro-inflammatory gene expression. A single intrathecal injection of sEVs derived from LPS stimulated RAW 264.7 cells attenuated mechanical hyperalgesia in the complete Freund’s adjuvant (CFA) mouse model of inflammatory pain and formalin induced acute pain. Importantly, sEVs did not alter the normal pain threshold in control mice. RNA sequencing of dorsal horn of the spinal cord showed sEVs-induced modulation of immune regulatory pathways. Further, a single prophylactic intrathecal injection of sEVs two weeks prior, attenuated CFA-induced pain hypersensitivity and was ineffective in formalin model. This indicates that prophylactic sEVs administration can be beneficial in attenuating chronic pain without impacting responses to the protective physiological and acute inflammatory pain. Prophylactic administration of sEVs could form the basis for a safe and novel vaccine-like therapy for chronic pain or as an adjuvant, potentially reducing the dose of drugs needed for pain relief. |
| Databáze: | OpenAIRE |
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