Analgesia produced by normal doses of opioid antagonists alone and in combination with morphine

In a recent study [30] it was reported that naloxone, at doses normally employed for opioid antagonism, produced a dose-dependent analgesia in BALB/c mice in the formalin test. We report here that another opioid antagonists, naltrexone, also produces analgesia under these conditions. Female BALB/c mice were injected subcutaneously with naltrexone (0.01-1.0 mg/kg) or saline alone and tested for analgesia using the formalin test. Naltrexone produced a statistically significant dose-dependent analgesia, with an ED50 of 0.05 mg/kg and almost total analgesia at doses of 0.1 mg/kg or greater. To determine the relationship between naloxone analgesia and better documented forms of opioid analgesia, BALB/c mice were injected with naloxone or saline following the administration of a pre-determined ED50 for morphine and tested for analgesia using the tail-flick and formalin tests. Naloxone antagonized morphine analgesia in the tail-flick test at both doses used (0.3 and 10 mg/kg). In the formalin test, however, naloxone attenuated morphine analgesia at the lower doses (0.1 and 0.3 mg/kg) and potentiated morphine analgesia at the highest dose (10 mg/kg). The implications of this finding are discussed.