β-Endorphin mediates radiation therapy fatigue.

Autor: Hermann AL; Cutaneous Biology Research Center, Department of Dermatology and Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.; Department of Oncotherapy, Doctoral School of Clinical Medicine, University of Szeged, Szeged, Hungary., Fell GL; Cutaneous Biology Research Center, Department of Dermatology and Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Kemény LV; Cutaneous Biology Research Center, Department of Dermatology and Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.; HCEMM-SU Translational Dermatology Research Group, Department of Physiology, Semmelweis University, Budapest, Hungary.; Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, Budapest, Hungary., Fung CY; Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA., Held KD; Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.; National Council on Radiation Protection and Measurements, 7910 Woodmont Ave, Suite 400, Bethesda, MD 20814, USA., Biggs PJ; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Rivera PD; Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.; Department of Pediatrics, Lurie Center for Autism, Massachusetts General Hospital for Children, Boston, MA 02421, USA.; Department of Biology, Hope College, Holland, MI 49423, USA., Bilbo SD; Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.; Department of Pediatrics, Lurie Center for Autism, Massachusetts General Hospital for Children, Boston, MA 02421, USA., Igras V; Cutaneous Biology Research Center, Department of Dermatology and Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Willers H; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Kung J; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Gheorghiu L; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Hideghéty K; Department of Oncotherapy, Doctoral School of Clinical Medicine, University of Szeged, Szeged, Hungary.; ELI-ALPS Non Profit Ltd., Szeged, Hungary., Mao J; MGH Center for Translational Pain Medicine, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Woolf CJ; FM Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA., Fisher DE; Cutaneous Biology Research Center, Department of Dermatology and Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2022 Dec 16; Vol. 8 (50), pp. eabn6025. Date of Electronic Publication: 2022 Dec 16.
DOI: 10.1126/sciadv.abn6025
Abstrakt: 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.
Databáze: MEDLINE