Table 3 The effect of sEVs on pain relief
From: Current aspects of small extracellular vesicles in pain process and relief
Published year | Model | Resources | sEVs method | Treatment method | Dose | Effects | Speculated mechanisms | Ref. |
|---|---|---|---|---|---|---|---|---|
2023 | CCI | huc-MSCs | Sequential centrifugation | i.t. | 5 µg on 2, 4, and 6 days after CCI surgery | Ameliorated mechanical allodynia and inhibited microglia | Encapsulated miR-99b-3p promoted microglial autophagy and inhibited inflammation | [145] |
2023 | CCI | huc-MSCs | Sequential centrifugation | i.t. | 5 µg on days 2, 4, and 6 after surgery | Ameliorated mechanical allodynia; inhibited microglial activation and restrained activation of the TLR2/MyD88/NF-κB signal | / | [143] |
2022 | Carrageenan-induced pain | CD206+ M2 macrophages | Gradient centrifugation | i.t. | 5 µl (100 µl sEVs from 10 × 107) | / | sEVs transferred mitochondria to sensory neurons | [21] |
2022 | SNI | hPMSCs | Gradient centrifugation | i.t. | 5 µg | Alleviated hind paw withdrawal threshold | Encapsulated miR-26a-5p regulated Wnt5a/Ryk/CaMKII/NFAT signal | [144] |
2022 | Tendinopathy | iMSCs | Gradient centrifugation | Local injection | 1 × 109 particles/ml once a week for 4 weeks | Alleviated hind paw withdrawal threshold; inhibited the activation of mast cells | / | [137] |
2021 | CFA | M1-type macrophages | Gradient centrifugation | i.t. | 1 µg, a single injection | Attenuated mechanical hyperalgesia | Anti-inflammatory miRNAs | [98] |
2021 | Formalin model | M0- and M1-type macrophages | Gradient centrifugation | i.t. | 1 µg, 48 h before formalin injection | Reduced the late-phase formalin-induced nociceptive response and spontaneous pain | / | [98] |
2021 | IR-pain model | Neurons | Gradient centrifugation | i.t. | 20 µg in 20 µl | Improved mechanical sensitivity and thermal allodynia | miR-126-3p-enriched Hypo-VSC sEVs modulated PIK3R2-mediated PI3K/Akt and NF-κB signaling pathways | [56] |
2021 | EPA | iMSCs | Gradient centrifugation | i.v. | 1 × 1010 particles weekly | Reversed pain behavior; reduced the overexpression of COX-2 | / | [146] |
2020 | OA | Rat BMSCs | Ultracentrifugation | Local injection | 40 µg/100 µl | Relieved pain; promoted cartilage repair and extracellular matrix synthesis | / | [138] |
2020 | CFA | RAW264.7 | Gradient centrifugation | Local injection | 20 µl (0.5 µg) | Increased thermal pain and mechanical pain thresholds | sEVs containing miR-23a-3p regulated HDAC2/NRF2 axis by decreasing USP5 expression | [97] |
2020 | SNL | huc-MSCs | Ultrafiltration | Local treatment | Wrapped around nerve | Improved withdrawal threshold and latency; ameliorated inflammatory microenvironment | / | [172] |
2020 | DNP | Mouse BMSCs | Gradient centrifugation | i.v. | 1 × 109 particles weekly for 8 weeks | Improved neurological outcomes; downregulated TLR4/NF-κB signaling pathway in the sciatic nerve tissues | / | [136] |
2019 | SNL | huc-MSCs | Ultrafiltration | i.t. | Single 1.2 mg/ml or continuous infusion (hourly dose: 1.2 mg) | Attenuated mechanical allodynia and thermal hyperalgesia; inhibited neuron and glial activation and inflammation | / | [135] |
2014 | CFA | RAW264.7 | Gradient centrifugation | Local injection | 20 µl (0.5 µg) | Relieve thermal hyperalgesia and paw swelling | / | [96] |
2005 | Collagen-induced arthritis | Dendritic cells | Gradient centrifugation | i.v. | 1 µg in 10 µl | Reduced paw swelling | / | [185] |