Effects of the pineal body and melatonin on sensitivity to pain in mice

Sensitivity to painful stimuli was measured by hot plate, writhing tests and electric caudal stimulation in mice. The mice were kept under light-dark 12/12 cycle with light out at 18:00 for at least 2 wk. Both basal analgesia and meperidine (pethidine)-induced analgesic effect exhibited parallel circadian rhythms, with the marked peak and through occurring at mid-dark and mid-light phases, respectively. The day-night differences in pain threshold 10 d after pinealectomy were not evident, especially in the loss of dark time augmentation of analgesic responses, but persisted in sham operated mice. Melatonin (MT) 50-200 mg/kg ip during light phase produced analgesic activity. MT 250 mg/kg ip resulted in a loss of the righting reflex. In pinealectomized mice, the pre-treatment of MT 5 mg/kg potentiated levels of analgesia induced by meperidine 10 mg/kg or morphine 5 mg/kg. It is possible that MT is one of the endogenous nocifensor inhibitors in CNS.