Contribution of Small Extracellular Vesicles from Schwann Cells and Satellite Glial Cells to Pain Processing
Abstract
:1. Introduction
1.1. Extracellular Vesicles (EVs)
1.1.1. CNS Glia-Derived EVs
Astrocyte-Derived Extracellular Vesicles (ADEVs)
Microglia-Derived Extracellular Vesicles (MGEVs)
Oligodendrocyte-Derived Extracellular Vesicles (ODEVs)
1.1.2. PNS-Derived EVs
Schwann Cell-Derived Extracellular Vesicles (SDEVs)
Satellite Glial Cell-Derived Extracellular Vesicles (SGC-Derived EVs)
1.2. Trigeminal SGC-Derived sEVs in an In Vitro Model Mimicking Inflammatory Pain In Vivo
1.2.1. miRNA Cargo
1.2.2. Protein Cargo
2. PNS Glial-Derived sEVs and Pain: Current Status and Challenges
3. Future Directions for sEVs in Pain
3.1. Biomarkers
3.2. Pain Relief through MSC-sEVs
- Local delivery in tendinopathy and osteoarthritis: The continuous local delivery of MSC-sEVs in rats mitigates tendinopathy-associated acute pain. MSC-sEVs reduce mast cell infiltration, lower proinflammatory cytokines, and alleviate osteoarthritis pain [58].
- Neuropathic pain interventions: UCMSC-sEVs demonstrate dose-dependent analgesic effects for those with neuropathic pain. The intrathecal administration of MSC-sEVs prevents neuropathic pain development and improves patients’ pain thresholds. Wrapped UCMSC-sEVs in an alginate scaffold provide prolonged antinociceptive effects and promote axon regeneration. MSC-sEVs influence neuron and glial activation, downregulate Rsad2 expression, and inhibit TLR2/MyD88/NF-κB signaling. Encapsulated miRNAs in MSC-sEVs, such as miR-26a-5p, miR-99b-3p, miR-190b-5p, and miR-152-3p, regulate microglia activation and suppress neuroinflammation [7,59].
- Diabetic peripheral neuropathy (DPN): The systemic administration of MSC-sEVs in a murine DPN model restored mechanical and thermal thresholds and caused M1-to-M2 macrophage phenotype shifting. MSC-sEVs enhance nerve conduction velocity and support the survival and axonal growth of injured neurons in DPN [7,60].
- Visceral pain and immunomodulation: MSC-sEVs alleviated chronic pelvic pain in an experimental autoimmune prostatitis (EAP) model [62] by modulating immune cell counts and reducing COX-2 overexpression. MSC-sEVs demonstrate therapeutic potential [7] for pain associated with inflammatory bowel disease (IBD) and cystitis by regulating immune responses and promoting the M2 macrophage phenotype.
3.3. Modification of sEVs for Targeted Pain Management
4. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gazerani, P. Contribution of Small Extracellular Vesicles from Schwann Cells and Satellite Glial Cells to Pain Processing. Neuroglia 2024, 5, 1-12. https://doi.org/10.3390/neuroglia5010001
Gazerani P. Contribution of Small Extracellular Vesicles from Schwann Cells and Satellite Glial Cells to Pain Processing. Neuroglia. 2024; 5(1):1-12. https://doi.org/10.3390/neuroglia5010001
Chicago/Turabian StyleGazerani, Parisa. 2024. "Contribution of Small Extracellular Vesicles from Schwann Cells and Satellite Glial Cells to Pain Processing" Neuroglia 5, no. 1: 1-12. https://doi.org/10.3390/neuroglia5010001