| First Author | Hermann AL | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 50 | Pages | eabn6025 |
| PubMed ID | 36525492 | Mgi Jnum | J:351327 |
| Mgi Id | MGI:7413610 | Doi | 10.1126/sciadv.abn6025 |
| Citation | Hermann AL, et al. (2022) beta-Endorphin mediates radiation therapy fatigue. Sci Adv 8(50):eabn6025 |
| abstractText | Fatigue is a common adverse effect of external beam radiation therapy in cancer patients. Mechanisms causing radiation fatigue remain unclear, although linkage to skin irradiation has been suggested. beta-Endorphin, an endogenous opioid, is synthesized in skin following genotoxic ultraviolet irradiation and acts systemically, producing addiction. Exogenous opiates with the same receptor activity as beta-endorphin can cause fatigue. Using rodent models of radiation therapy, exposing tails and sparing vital organs, we tested whether skin-derived beta-endorphin contributes to radiation-induced fatigue. Over a 6-week radiation regimen, plasma beta-endorphin increased in rats, paralleled by opiate phenotypes (elevated pain thresholds, Straub tail) and fatigue-like behavior, which was reversed in animals treated by the opiate antagonist naloxone. Mechanistically, all these phenotypes were blocked by opiate antagonist treatment and were undetected in either beta-endorphin knockout mice or mice lacking keratinocyte p53 expression. These findings implicate skin-derived beta-endorphin in systemic effects of radiation therapy. Opioid antagonism may warrant testing in humans as treatment or prevention of radiation-induced fatigue. |
