Morphine analgesia and acute physical dependence: rapid onset of two opposing, dose-related processes

Enhanced responsiveness to noxious stimulation is a reliable sign of opioid withdrawal and is therefore a measure of physical dependence. In lightly anesthetized rats, naloxone, given i.v. 15 min following i.v. morphine, caused a significant shortening of tail flick latency (hyperalgesia). At each dose of naloxone (0.1, 1.0 or 2.0 mg/kg), the magnitude of the observed hyperalgesia was a function of the preceding dose of morphine (0.5, 1.0 or 2.0 mg/kg). Thus morphine rapidly induces two dose-related opposing processes: one results in antinociception and the other in the potential for hyperalgesia.