ANALGESIA PRODUCED BY A SPINAL ACTION OF MORPHINE AND EFFECTS UPON PARTURITION IN THE RAT

Opiates adminitered into the lumbar spinal subarachnoid spaces of rats and rabbit through indwelling catheters produce dose-dependent analgesia. In the present experiments, such injections were made on the day of partitution in gravid female rats and rabbits. In rats, intrathecal injections of morphine sulfate, 15, 45, or 100 μg, were made at intervals such that significant analgesia, as measured by the tail-flick and hot-plate tests, would be maintained until partitution occurred. The injections had no detectable effect on onset of partitution, per cent of the litter alive after one hour, or respiratory rate of either the mother or the newborn. In contrast, morphine, 3, 10, or 20 mg/kg, administered subcutaneously, 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 hours as measured by block of the skin twitch response. Such injections, however, 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 an hour after morphine injection) to 10 ng/ml (delivery occurring eight hours after morphine injection). Newborn plasma levels ranged from 0 to 2 ng/ml in the first four hours after intrathecal injection in the mother to 10 ng/ml when the delivery occurred eight hours after intrathecal injection in the mother. These data support previous work indicating the significant analgesia and the lack of effect upon respiratory rate and motor function of intrathecal morphine. They further demonstrate that intrathecal administration has no detectable effect on the initiation of gestation and the viability of the newborn or its repiratory rate.