The protective effect of bergamot derived flavonoid on the post-translational modulationof glutamate transmission: a new therapeutic approach for opioid tolerance management

Opiates like morphine sulfate are the most effective analgesics for treating acute and chronic severe pain such as cancer pain, but their use is limited by the development of tolerance and hypersensitivity to inocuous and noxious stimuli. We have demonstrated a role for superoxide-derived peroxynitrite (ONOO) to cause opiate-induced hyperalgesia and antinociceptive tolerance. Our data reiforce the important rolew of nitroxidative species in opiate tolerance ans suggest novel therapeutic approach in the management of chronic pain, in particular for those patients who require long-term opioid treatment for pain relief without development of tolerance.