The Circadian Hormone Melatonin Inhibits Morphine-Induced Tolerance and Inflammation via the Activation of Antioxidative Enzymes.

Dysregulated circadian light exposure significantly compromises the efficacy of morphine's antinociceptive effect, while the cotreatment with melatonin attenuates morphine tolerance/hyperalgesia development. Our results suggest the potential of melatonin as an adjuvant of morphine in clinical pain management, particularly in patients who need long-term opioid treatment.