Opiates are the most effective treatment for acute and chronic severe pain. However, for the fact that they
provoke the development of analgesic tolerance as observed in human studies, their clinical utility is often lower.
Morphine is a principal opiate, but to get an equivalent pain relief with it, the doses of administration need to be
constantly increasing. However, such dose increase has a therapeutic impact by on setting morphine-induced hypersensitivity.
This complex pathophysiological cycle contributes significantly to decreased quality of life in the population
of subjects with chronic pain. In any case, interests in new approaches that would maintain opiate efficacy during
repetitive dosing without engendering tolerance or unacceptable side-effects are growing.
Recent evidence has implicated oxidative stress in the development of pain in several pathologies and most importantly in
opiate antinociceptive tolerance, caused by the presence of free radicals. This mini-review on some opioids and their
possible mechanisms has dual objective: to discuss the importance and role of free radicals in maintenance of pain and
induction of opiate antinociceptive tolerance; and to demonstrate that opiates are rational target for therapeutic intervention
in pain management, as well as to provide a pharmacological basis for developing inhibitors of free radical