Analgesia Produced by a Spinal Action of Morphine and Effects upon Parturition in the Rat

Abstract

Opiates administered into the lumbar spinal subarachnoid spaces of rats and rabbits through indwelling catheters produce dose-dependent analgesia. Injections were made on the day of parturition in gravid female rats and rabbits. In rats, intrathecal injections of morphine sulfate 15, 45 or 100 .mu.g were made at intervals such that significant analgesia as measured by the tail-flick and hot-plate tests would be maintained until parturition occurred. The injections had no detectable effect on onset of parturition, percent of the litter alive after 1 h, or respiratory rate of either the mother or the newborn. In contrast, morphine 3, 10 or 20 mg/kg administered s.c., produced a dose-dependent decrease in newborn respiratory rates and an increase in the number of rat pups dead within the hour after birth. In rabbits, intrathecal injection of morphine 80 mg produced prolonged antinociception for 12-14 h as measured by block of the skin twitch response. Such injections failed to delay the onset of delivery or alter the interval between births in a litter. Respiratory rates and general appearances of newborn rabbits whose mothers had received intrathecal morphine were not different from those of controls. Plasma levels of morphine in mother and newborn were assayed at birth. Plasma morphine levels in the mothers ranged from 30 ng/ml (delivery occurring 1 h after morphine injection) to 10 ng/ml (delivery occurring 8 h after morphine injection). Newborn plasma levels ranged from 0-2 ng/ml in the first 4 h after intrathecal injection in the mother to 10 ng/ml when the delivery occurred 8 h after intrathecal injection in the mother. Intrathecal administration has no detectable effect on the initiation of gestation and the viability of the newborn or its respiratory rate.