Publications [#368470] of Staci D. Bilbo

Journal Articles

1. Hermann, AL; Fell, GL; Kemény, LV; Fung, CY; Held, KD; Biggs, PJ; Rivera, PD; Bilbo, SD; Igras, V; Willers, H; Kung, J; Gheorghiu, L; Hideghéty, K; Mao, J; Woolf, CJ; Fisher, DE (2022). β-Endorphin mediates radiation therapy fatigue.. Science advances, 8(50), eabn6025. [doi]
   (last updated on 2025/06/16)

   Abstract:
   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. β-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 β-endorphin can cause fatigue. Using rodent models of radiation therapy, exposing tails and sparing vital organs, we tested whether skin-derived β-endorphin contributes to radiation-induced fatigue. Over a 6-week radiation regimen, plasma β-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 β-endorphin knockout mice or mice lacking keratinocyte p53 expression. These findings implicate skin-derived β-endorphin in systemic effects of radiation therapy. Opioid antagonism may warrant testing in humans as treatment or prevention of radiation-induced fatigue.