ArticleBrain, behavior, and immunity2021
Therapeutic and prophylactic effects of macrophage-derived small extracellular vesicles in the attenuation of inflammatory pain.
Article in Brain, behavior, and immunity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 38 citations in OpenAlex.
- Markers and Enrichment Strategies for Brain-Derived Extracellular Vesicles: Current Evidence, Limitations and Future Directions.Neuromolecular medicine · 2026Review
- Catecholamine-mediated release of miR-133a-3p from adipocytes regulates the onset of chronic primary pain.The Journal of clinical investigation · 2026Article
- Macrophage-derived extracellular vesicles promote T cell-dependent inflammatory pain resolution.bioRxiv : the preprint server for biology · 2026Article
- Microglial epigenetic memory is associated with accelerated resolution of inflammatory pain induced by prophylactic macrophage-derived small extracellular vesicles.bioRxiv : the preprint server for biology · 2026Article
- Protectin DX resolves fracture-induced postoperative pain in mice via neuronal signaling and GPR37-activated macrophage efferocytosis.The Journal of clinical investigation · 2026Article
- Microglial Epigenetic Memory is Associated with Accelerated Resolution of Inflammatory Pain Induced by Prophylactic Macrophage-Derived Small Extracellular Vesicles.Journal of inflammation research · 2026Article
- Source-Specific Extracellular Vesicle Functions and Engineering Strategies for Chronic Pain Management: A Comprehensive Review.International journal of nanomedicine · 2026Review
- Morphine-induced hyperalgesia impacts small extracellular vesicle microRNA composition and function.The Journal of pharmacology and experimental therapeutics · 2025Article
- Unveiling the Mechanisms of Pain in Endometriosis: Comprehensive Analysis of Inflammatory Sensitization and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Inflammatory pain resolution by mouse serum-derived small extracellular vesicles.Brain, behavior, and immunity · 2025Article
- Diverse-Origin Exosomes Therapeutic Strategies for Diabetic Wound Healing.International journal of nanomedicine · 2025Review
- miRNA packaging into small extracellular vesicles and implications in pain.Pain reports · 2024Review
- miR-374 family is a key regulator of chronic primary pain onset.Pain reports · 2024Article
- Role of Exercise on Inflammation Cytokines of Neuropathic Pain in Animal Models.Molecular neurobiology · 2024Review
- The Immune-Centric Revolution Translated into Clinical Application: Peripheral Blood Mononuclear Cell (PBMNC) Therapy in Diabetic Patients with No-Option Critical Limb-Threatening Ischemia (NO-CLTI)-Rationale and Meta-Analysis of Observational Studies.Journal of clinical medicine · 2024Review
- Morphine-induced hyperalgesia impacts small extracellular vesicle miRNA composition and function.bioRxiv : the preprint server for biology · 2024Article
- Neural and immune roles in osteoarthritis pain: Mechanisms and intervention strategies.Journal of orthopaedic translation · 2024Review
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- Santacruzamate A Alleviates Pain and Pain-Related Adverse Emotions through the Inhibition of Microglial Activation in the Anterior Cingulate Cortex.ACS pharmacology & translational science · 2024Article
- Inflammatory pain resolution by mouse serum-derived small extracellular vesicles.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.