Restraint-induced analgesia in the CD-1 mouse: interactions with morphine and time of day

The tail-flick response of adult male CD-1 mice was used to assess the analgesic properties of restraint alone and in combination with morphine during the diurnal and nocturnal periods. Mice were restrained in conical metal devices that allowed a change in position from supine to prone but not from front to back. Restraint induced an analgesia equipotent to a 2.5 mg/kg dose of morphine within 0.5 h of its initiation. Although habituation occurred over the restraint period a pronounced analgesia was still evident at the end of the 3 h test period. The habituation to restraint-induced analgesia was more rapid at night. Although the basal tail-flick latency to thermal stimulation was decreased during the nocturnal period the time of day did not alter the degree of analgesia induced by either restraint or morphine. Morphine induced a dose- and time-dependent analgesia during both the diurnal and nocturnal periods and this analgesia was potentiated by restraint stress only during the nocturnal period. Naloxone at high doses (10.0 or 20.0 mg/kg) blocked the analgesia induced by morphine but did not totally block the analgesia induced either by restraint or morphine plus restraint. These data suggest the potentiation of an opiate effect by stress may depend on habituation or tolerance to the stressor.