Antinociception induced by simultaneous intrathecal and intraperitoneal administration of low doses of morphine

The application of morphine simultaneously into the spinal cord and brain ventricles produces a supraadditive antinociceptive effect. In this study, we attempted to determine whether combined intrathecal (IT) and intraperitoneal (IP) administration of small doses of morphine also produces such a synergistic antinociceptive effect. The experiments were performed on male Wistar rats. Nociception was measured using the tail immersion test. For IT administration morphine was injected through a catheter implanted in the subarachnoid space. Combined administration of small doses of IT (1 microgram) and IP (1 mg/kg) morphine resulted in a strong, highly significant antinociceptive effect. This effect was not only much higher than that produced by separate administration of the same doses of morphine, but also much higher than the expected effect of the combination. These results demonstrate that low doses of IT and IP morphine interact in a supraadditive fashion to produce potent analgesia.