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 administration of morphine could block the development of hyperalgesia and allodynia in a rat model of osteotomy or bone damage. METHODS: Withdrawal responses to mechanical and thermal stimuli applied to the plantar surface of the hind paw were measured before and after bone damage. The bone was injured by drilling a 1-mm hole through the tibia during short-lasting general anesthesia. In separate groups of rats, the effects of administering morphine (20-80 microg), either into the marrow cavity or systemically, on the development of hyperalgesia and allodynia after bone 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 microg). RESULTS: In animals that received no drug treatment, hyperalgesia and allodynia peaked 2 h after injury. Injection of morphine (40 and 80 microg) into the marrow cavity immediately after bone injury prevented the development of hyperalgesia and allodynia. Clocinnamox (0.15 mg) injected into the marrow cavity before administration of morphine blocked the antihyperalgesic effect of morphine. CONCLUSION: This study shows that local application of a low dose of morphine effectively blocks the development of hyperalgesia and allodynia in a rat model of bone damage through mu-opioid receptor action. These findings provide further evidence that local application of morphine at the time of orthopedic surgery, bone graft, or bone marrow harvesting may reduce the amount of postoperative pain.