β-Endorphin mediates radiation therapy fatigue.

Area of Science:

• Oncology
• Pharmacology
• Neuroscience

Background:

• Fatigue is a frequent side effect of radiation therapy.
• The underlying mechanisms of radiation-induced fatigue are not fully understood.
• Skin irradiation has been proposed as a potential contributor to radiation fatigue.

Purpose of the Study:

• To investigate the role of skin-derived beta-endorphin (β-endorphin) in radiation-induced fatigue.
• To explore the potential of opioid antagonism as a countermeasure for radiation fatigue.

Main Methods:

• Utilized rodent models for radiation therapy, focusing on tail exposure.
• Administered opiate antagonist naloxone to assess its effects on radiation-induced phenotypes.
• Examined beta-endorphin (β-endorphin) levels, opiate-related behaviors, and fatigue-like symptoms.
• Conducted experiments with beta-endorphin knockout mice and mice lacking keratinocyte p53 expression.

Main Results:

• Radiation therapy increased plasma beta-endorphin (β-endorphin) levels in rats.
• Observed opiate phenotypes and fatigue-like behaviors that were reversed by naloxone treatment.
• Blocked all radiation-induced phenotypes in beta-endorphin knockout mice or mice lacking keratinocyte p53 expression.

Conclusions:

• Skin-derived beta-endorphin (β-endorphin) plays a significant role in systemic effects of radiation therapy, including fatigue.
• Opioid antagonism, such as with naloxone, shows promise for treating or preventing radiation-induced fatigue in cancer patients.