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- W4309482926 abstract "Fatigue is a common adverse effect of external beam radiation therapy in cancer patients. Mechanisms that lead to radiation fatigue remain unclear. However, previously fatigue has been linked to skin irradiation. It has been previously established that β-endorphin, an endogenous opioid, is synthesized in skin following genotoxic UV irradiation. An increase in peripherally synthetized endorphin can have systemic effects to produce multiple opioid phenotypes, like addicitive behavior. Exogenous opioids with the same receptor activity as β-endorphin can cause fatigue. We used rodent models of radiation therapy, exposing tails and sparing vital organs, and we tested whether skin-derived β-endorphin may contribute to radiation-induced fatigue-like behavior. Over a 6-week radiation regimen, plasma β-endorphin increased in rats, paralleled by opiate phenotypes and fatigue-like behavior. Importantly, fatigue-like behavior was reversed in animals treated by the opiate antagonist naloxone. To investigate the mechanism leading to elevated skin-derived endorphin synthesis, we utilized genetic mouse models and found that all opioid phenotypes triggered by ioinizing radiation were blocked by opiate antagonist treatment and were undetected in either β-endorphin knockout mice or mice lacking keratinocyte p53 expression. Collectively, our results implicate the role of skin-derived β-endorphin in systemic effects of radiation therapy. Furthermore, our results suggest that opioid antagonism may warrant testing in humans as treatment or prevention of radiation-induced fatigue." @default.
- W4309482926 created "2022-11-28" @default.
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- W4309482926 date "2022-12-01" @default.
- W4309482926 modified "2023-09-25" @default.
- W4309482926 title "531 Skin-derived beta-endorphin mediates radiation therapy fatigue" @default.
- W4309482926 doi "https://doi.org/10.1016/j.jid.2022.09.546" @default.
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