PERIPHERAL MORPHINE ADMINISTRATION BLOCKS THE DEVELOPMENT OF HYPERALGESIA AND ALLODYNIA AFTER BONE DAMAGE IN THE RAT

Background The current study aimed to assess whether local administrat ion of morphine could block the development of hyperalgesia and allody nia in a rat model of osteotomy or bone damage. Methods: Withdrawal re sponses to mechanical and thermal stimuli applied to the plantar surfa ce of the hind paw were measured before and after bone damage. The bon e was injured by drilling a 1-mm hole through the tibia during short-l asting general anesthesia. In separate groups of rats, the effects of administering morphine (20-80 mu g), either into the marrow cavity or systemically, on the development of hyperalgesia and allodynia after b one damage were assessed. In an additional group of rats, a selective mu-opioid receptor antagonist, clocinnamox (0.15 mg), was administered into the marrow cavity before the administration of morphine (40 mu g ). Results: In animals that received no drug treatment, hyperalgesia a nd allodynia peaked 2 h after injury, Injection of morphine (40 and 80 mu g) into the marrow cavity immediately after bone injury prevented the development of hyperalgesia and allodynia. Clocinnamox (0.15 mg) i njected into the marrow cavity before administration of morphine block ed the antihyperalgesic effect of morphine.Conclusion: This study show s that local application of a low dose of morphine effectively blocks the development of hyperalgesia and allodynia in a rat model of bone d amage through mu-opioid receptor action. These findings provide furthe r evidence that local application of morphine at the time of orthopedi c surgery, bone graft, or bone marrow harvesting may reduce the amount of postoperative pain.