Effects of intrathecal orphanin FQ on the development of tolerance to morphine analgesia in unanaesthetic rats and on the antinociception in morphine-tolerance rats

Objectives:To observe whether OFQ has the delaying effects on the development of tolerance to morphine analgesia,and whether there is a cross tolerance between the antinociceptive effects of i.t. OFQ and the μ opioid receptor agonist morphine. Methods: A variety dose of OFQ and morphine was microinjected intrathecally in rats, the pain threshold was measured by using tail flick test, and the changes of antinociceptive effects after intrathecal OFQ/morphine on the rats tolerant acutelly or chronically to morphine/OFQ were observed. Results:OFQ microinjected intrathecaliy delayed the development of chronic tolerance to morphine analgesia, and had no effects on the development of acute tolerance to morphine analgesia, there had no cross tolerance between OFQ and morphine in eliciting spinal antinociception. Conclusions:The effects of OFQ delaying the development of tolerance to morphine analgesia may occur with the changes of G protein AC cAMP system, and/or with reducing dopamine release in the nucleus accumbens, lack of cross tolerance between the antinociceptive effects of i.t. OFQ and morphine indicates that the mechanism of tolerance to OFQ maybe different from that of morphine.