Table 2.
Signal transduction in spinal cord microglia and astrocytes after tissue and nerve injury.
Painful tissue and nerve injuries induce release of glial activators, which in turn bind their respective receptors on microglia and astrocytes. Upon activation, the glial receptors cause intracellular signal transduction and activation of protein kinases (phosphorylation of MAP kinase and SRC kinase), leading to increased synthesis and release of glial mediators that can produce central sensitization and hyperalgesia and allodynia.
| Microglia | Astrocytes |
|---|---|
| Activators | Activators |
| ATP | ATP |
| CX3CL1 | TNF |
| CSF1 | CXCL13 |
| LPS/HMGB1 | LPS/HMGB1 |
| CASP6 | MMP-2 |
|
| |
| Receptors | Receptors |
| P2X4, P2X7, P2Y12 | P2X/P2Y |
| CX3CR1 | TNFR1 |
| CSF1R | CXCR5 |
| TLR4 | TLR4 |
| C5aR | Cx43 |
|
| |
| Intracellular signaling | Intracellular signaling |
| P-P38, P-ERK, P-SRC | P-JNK, P-ERK |
|
| |
| Mediators | Mediators |
| TNF | CCL2, CXCL1 |
| IL-1β, IL-18 | TSP1, TSP4 |
| BDNF | bFGF, IL-1β |
Abbreviations: bFGF-2, basic fibroblast growth factor 2; CASP6, caspase 6, CSF1; colony stimulating factor 1; CXCL13, chemokine (C-X-C motif) ligand 13, Cx43, connexin-43; C5aR, complement C5 receptor; HMGB1, high motility group box protein 1; LPS, lipopolysaccharide; MMP-2, matrix metalloprotease-2; TLR4, toll-like receptor 4; TNF, tumor necrosis factor (alpha); TNFR, TNF receptor; TSP-1, thromspondin-1; TSP-4, thromspondin-4.