TABLE 1.
Summary of EGFR ligands and their implicated actions in pain.
| Ligand | Receptor(s) | Evaluated nocifensive stimuli | Mechanistic findings | Implicated human pain conditions | References |
|---|---|---|---|---|---|
| High affinity ligands | |||||
| EGF | EGFR | Mechanical | GRK2 phosphorylation; opioid receptor downregulation | Opioid tolerance | Chen et al. (2008), Puig et al. (2020) |
| BTC | EGFR, HER4 | — | — | — | — |
| HB-EGF | EGFR, HER4 | Mechanical | ↑ DRG neuron intracellular Ca2+ | RA | Wangzhou et al. (2021) |
| TGFα | EGFR | — | — | Pancreatic cancer | Wangzhou et al. (2021) |
| Low affinity ligands | |||||
| AREG | EGFR | — | — | — | — |
| EREG | EGFR, HER4 | Heat; capsaicin; mechanical; formalin | PI3K-Akt-mTORC1 signaling activation; ↑ spontaneous C fibre firing; ↑ capsaicin-evoked DRG neuron intracellular Ca2+ | RA; radiculopathy; peripheral nerve injury | Huang et al. (2017), Martin et al. (2017), Kongstorp et al. (2019), Wangzhou et al. (2021) |
| EPGN | EGFR | — | — | — | — |
Experimental evidence for and suggested roles of EGFR ligands in pain. Evaluated nocifensive stimuli, mechanistic findings and human conditions in which ligands have been implicated to contribute to pain are indicated. EGF: epidermal growth factor, BTC: betacellulin, HB-EGF: heparin-binding epidermal growth factor-like growth factor, TGFα: transforming growth factor alpha, AREG: amphiregulin, EREG: epiregulin, EPGN: epigen. PGE2: prostaglandin E2. i. t.: intrathecal, DRG: dorsal root ganglion, RA: rheumatoid arthritis, SNI: spared nerve injury, CFA: complete Freund’s adjuvant. — indicates no available data.