Background: The aim of this study was to evaluate the efficacy of chronic oral administration of morphine in physical dependence, hyperalgesia, and tolerance to analgesic effect of morphine using the formalin test.

Materials and Methods: In this study, 40 male Wistar rats received sucrose and the morphine+sucrose in drinking water for 20 days. On the 20th day, after intraperitoneal injection of naloxone, the withdrawal symptoms were assessed. Next day, the analgesic effect of morphine injection in various doses was analyzed based on behavioral responses in formalin test in both morphine+sucrose and sucrose-treated groups.

Results: Statistical analysis showed that there is a significant difference in some symptoms of the physical dependence between the two groups. Although morphine, in sucrose-treated rats, caused a dose-dependent reduction in pain score in both phases of formalin test, it did not have any significant analgesic effect on the morphine+sucrose treated rats.

Conclusion: Although the oral morphine administration induces tolerance to the analgesic effect of morphine and physical dependence, it does not develop hyperalgesia as a characteristic of addictive behaviors in clinical settings.