Lack of antinociceptive cross-tolerance with co-administration of morphine and fentanyl into the periaqueductal gray of male Sprague-Dawley rats

Morphine and fentanyl are two of the most commonly used drugs to treat pain. Chronic use is limited by unpleasant side effects and the development of tolerance. Opioid rotation and co-administration have been used to enhance pain relief and limit these side effects28,44. Although animal studies report additive antinociceptive effects when morphine and fentanyl are co-administered5,39, clinical research indicates that the analgesic efficacy of co-administered morphine and fentanyl is greater than administration of either opioid alone28,47.

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