Effects of melatonin, morphine and diazepam on formalin-induced nociception in mice

The possible analgesic effect of melatonin was investigated in young male I CR mice. The formalin test which elicits typically 2 phases of pain respons e, the acute (first) phase and tonic (second) phase, was used. The test was performed in the late light period when the;mice have been reported to be more sensitive to pain. Compared to control mice, no significant difference in nociceptive response was observed when melatonin was injected intraperi toneally at doses of 0.1, 5, and 20, mg/kg body weight. The combined effect s of melatonin with diazepam and/or morphine, were also investigated. Melat onin, injected at 20 mg/kg 15 min before formalin test, significantly incre ased the antinociceptive response of diazepam (1 mg/kg) or morphine (5 mg/k g) in the second phase. In addition, when melatonin was given at 20 mg/kg t ogether with diazepam and morphine, antinociceptive responses in both the f irst and second phase were increased. These data indicate the synergistic a nalgesia effect of melatonin with morphine and diazepam and suggest the pos sible involvement of melatonin as an adjunct medicine for pain patients. (C ) 2001 Elsevier Science Inc. All rights reserved.