Table 2.
Anti-inflammatory mechanisms of SPMs in chronic pain.
| SPMs | Endogenous sources | Exogenous sources | Anti-inflammatory mechanisms | Refs |
|---|---|---|---|---|
| Resolvin D1 (RvD1) | Neutrophils, macrophages, and platelets | Docosahexaenoic (DHA) | ♦ Promotes resolution of inflammation | 25–29 |
| ♦ Decreases inflammatory response and apoptosis | ||||
| ♦ Protects the endothelial integrity and barrier function | ||||
| ♦ Inhibits the activity of TRPA1, TRPV3, and TRPV4 | ||||
| Resolvin D2 (RvD2) | Macrophages, epithelial cells, and platelets | ♦ Decreases inflammatory response | 30–33 | |
| ♦ Inhibits the activity of TRPV1 and TRPA1 | ||||
| ♦ Increases the production of anti-inflammatory mediator TGF-β1 | ||||
| ♦ Transforms the macrophages from inflammatory to anti-inflammatory phenotype | ||||
| Resolvin D3 (RvD3) | Macrophages and neutrophils | ♦ Inhibits the activity of TRPV1 and CGRP release via a G-protein coupled receptor, such as ALX/FPR2 | 34,35 | |
| ♦ Decreases the inflammatory cytokines and chemokines, such as TNF-α, IL-6, IL-1β, CCL2, and CCL3 | ||||
| Resolvin D4 (RvD4) | Neutrophils, macrophages, and dendritic cells | ♦ Decreases the inflammatory response | 36 | |
| Resolvin D5 (RvD5) | Neutrophils, macrophages, and platelets | ♦ Decreases the expression of IL-6 in male mice with chronic pain | 37 | |
| Resolvin D6 (RvD6) | Neutrophils and macrophages | ♦ Increases the expression of rictor and hepatocyte growth factor (hgf) and rictor genes | 38 | |
| Resolvin E1 (RvE1) | Neutrophils, eosinophils, platelets, and epithelial cells | Eicosapentaenoic (EPA) | ♦ Inhibits the migration of neutrophils to inflammatory site | 39,40 |
| ♦ Decreases the release of TNF-α, IL-1β, and IL-6 | ||||
| Resolvin E2 (RvE2) | Macrophages and dendritic cells | ♦ Inhibits neutrophil infiltration | 40 | |
| ♦ Decreases the expression of pro-inflammatory cytokines | ||||
| Resolvin E3 (RvE3) | Neutrophils and endothelial cells | ♦ Inhibits inflammatory activity | 41 | |
| Maresin 1 (MaR-1) | Macrophages | DHA | ♦ Blocks NLRP3 inflammasome | 42,43 |
| ♦ Shifts from M1 macrophages to M2 phenotype | ||||
| Maresin 2 (MaR-2) | ♦ Blocks neutrophil and monocyte migration | 44 | ||
| ♦ Inhibits the activity of TRPA1, and the release of CGRP | ||||
| Protectins D1 | Neutrophils | DHA | ♦ Inhibits T cell infiltration | 45–47 |
| ♦ Reduces neutrophil recruitment | ||||
| Neuroprotection D1 | Epithelial cells | ♦ Decreases inflammatory response | ||
| Lipoxins | Leukocytes, platelets, endothelial cells, and fibroblasts | Arachidonic acid (AA) | ♦ Inhibits pro-inflammatory mediator production | 48,49 |
| ♦ Blocks neutrophils infiltration |