Effects on long-term sensitivity to pain and morphine of stress induced in the newborn rat by pain or manipulation.

Four times daily from postnatal day 1 to 15, rats were stressed either by being removed from the maternity cage (manipulation stress, MS) or by being placed on a hotplate at 55 degrees C (pain stress, PS). When 70 days old, they were examined for sensitivity to pain and to the analgesic effect of morphine, and for brain opiate receptors. Pain sensitivity of MS and PS rats was not significantly different from that of controls. The analgesic activity of morphine, assessed by the hotplate test at 49 degrees C, was significantly reduced in MS rats, while in PS rats it was similar to that in controls. 3H-dihydromorphine binding studies performed on whole brain synaptic membranes showed a reduction in the maximum number of binding sites in both MS and PS rats; on the other hand, the affinity constant was higher in PS rats, while in MS rats it was similar to that of controls. These data show that the repeated stress of removal from the mother during the first 15 days of life induce a reduction in the number of brain opiate receptors with reduced activity of morphine, while in rats exposed to repeated removal stress associated with painful stimuli the reduction in the number of brain opiate receptors seems to be counterbalanced by their higher affinity.