Table 1.
Role of Exo in the alleviation of pain in the experimental settings.
| Model | Year | Exo source | Target cells or tissues | Outcome | Ref |
|---|---|---|---|---|---|
| In vitro model of osteoarthritis | 2020 | Bone marrow MSCs | IL-1β-treated chondrocytes | Chondrocyte Migration↑, Proliferation↑, COL2A1↑ and ACAN↑, ADAMTS5↓, MMP13↓ | (Console et al., 2019) |
| In vivo rat model of osteoarthritis induced by sodium iodoacetate | 2020 | Bone marrow MSCs | Knee joint | Reduced neuropathic pain via CGRP↓ and iNOS↓, improved PWL values | (Console et al., 2019) |
| Plasma exchange in patients with complex regional pain syndrome | 2019 | Plasma Exo miRNAs | Blood | hsa-miR-338-5p↓, IL-6↓, Inflammation↓ | (Shiue et al., 2019) |
| Administration of alginate-loaded Exo in rats with mechanical allodynia and thermal hyperalgesia | 2020 | Human umbilical MSCs | Right L5/6 spinal nerve | Withdrawal threshold and latency↑, Fos↓, GFAP↓, Iba1↓, TNF-α↓ and IL-1β↓, GDNF↑, Antinociceptive properties↑, Inflammation↓ | (Zhang et al., 2019) |
| Intrathecal injection of Exo in rats with nerve injury-induced neuropathic pain | 2019 | Human umbilical MSCs | L5/6 spinal nerve | Mechanical and thermal hypersensitivities↓, Pain↓, c-Fos↓, CNPase↓, GFAP↓, and Iba1↓, TNF-α↓ and IL-1β↓, IL-10↑, | (Zhou et al., 2021) |
| Application of Exo in rat model of osteoarthritis | 2019 | MSCs | Temporomandibular joint | Pain↓, Degeneration↓, Inflammation↓, Subchondral bone formation↑, | (Jean-Toussaint et al., 2021) |
| In vitro exposure of Exo with chondrocytes | 2019 | MSCs | Chondrocytes | Akt/Erk/AMPK↑, s-GAG synthesis↑, IL-1β↓, iNOS↓, MMP13↓ | (Jean-Toussaint et al., 2021) |
| Different doses of Exo in a rat model of osteoarthritis induced by monoiodoacetate-induced | 2021 | MSCs | knee joint | PWT and PWL values↑, GAP-43↑, ATF-3↓, Dose-dependent regeneration activity↑, Pain relief↑ | (Simeoli et al., 2017) |
| Macrophages Exo | 2021 | mouse RAW 264.7 macrophages-induced by lipopolysaccharide | Cortical neurons, Microglia, and Astrocytes | Pro-inflammatory miRNA↓ | (Moen et al., 2017) |
| Acute mouse model of acute inflammation induced by formalin | 2021 | mouse RAW 264.7 macrophages-induced by lipopolysaccharide | A single intrathecal injection | Mechanical hyperalgesia↓, prophylactic pain relief↑ | (Moen et al., 2017) |
| Dorsal root ganglia sensory neurons treated with capsaicin | 2020 | Exposure of macrophages to miR-21-5p antagomir-loaded Exo | Cell culture | Macrophage NOS2↓, Spry2↓, | (Simeoli et al., 2017) |
| Enhanced spinal cord nociceptive responses in rat model using placing nucleus pulposus onto dorsal nerve roots (Vertebraes Th13-L1, and L3–S1) | 2017 | Nucleus pulposus grafts Exo | Dorsal nerve roots | miR-223↑, Nociceptive spinal signaling↓, | (Moen et al., 2017) |
Mesenchymal stem cells: MSCs; Aggrecan: ACAN; ADAM Metallopeptidase With Thrombospondin Type 1 Motif 5: ADAMTS5; Type II collagen: COL2A1; Matrix metalloproteinases-13: MMP13; Calcitonin Gene-Related Peptide: CGRP; Inducible nitric oxide synthase: iNOS; Paw withdrawal latency: PWL; Glial Cell Derived Neurotrophic Factor: GDNF; Ionized calcium binding adaptor molecule 1: Iba1; Fos Proto-Oncogene, AP-1 Transcription Factor Subunit: FOS; Glial fibrillary acidic protein: GFAP; Sulfated glycosaminoglycan: s-GAG; Growth Associated Protein 43: GAP-43; Cyclic AMP-dependent transcription factor: ATF-3; Nitric Oxide Synthase 2: NOS2; Sprouty RTK Signaling Antagonist 2: Spry2.