The effects of epidural bupivacaine, morphine, and their combination on thermal nociception with different stimulus intensity in rats

The analgesic effect of drugs depends on the stimulus intensity as well as the potency of the drugs. We investigated the effects of stimulus intensity on antinociceptive potencies of epidural bupivacaine + morphine. Sprague-Dawley rats implanted with chronic lumbar epidural catheters were tested for paw withdrawal response to thermal stimulation after the epidural injection of bupivacaine, morphine, or bupivacaine + morphine. Two stimulation currents were used, 5.1 and 4.6 A, to provide baseline response latency of approximately 5.0 s (high intensity) and 10.0 s (low intensity), respectively. Increasing the dose of epidural morphine in a dose range that had a maximum effect on low-intensity stimulation was not effective for high-intensity stimulation. Bupivacaine, which alone had no effect, potentiated the antinociceptive effect of epidural morphine at both high- and low-intensity stimuli similarly. We concluded that bupivacaine potentiated the analgesic effect of epidural morphine at both weak and strong nociceptive stimuli similarly, whereas increasing the dose of epidural morphine was not as effective for strong nociceptive stimulation. Therefore, adding bupivacaine might be more effective than increasing the dose of epidural morphine for intense nociception.