Antinociceptive Synergy Between Intrathecal Morphine and Lidocaine during Visceral and Somatic Nociception in the Rat

Abstract

Clinical investigations have suggested a synergistic interaction between the analgesic effects of intrathecal opioids and local anesthetics; however, basic pharmacologic evidence for this observation has not been reported. Therefore, the authors have used models of visceral and somatic nociception to quantify the interaction between intrathecal morphine and lidocaine in a crossover study of 24 rats in four equal groups. Combinations of morphine and lidocaine were administered separately, corresponding to time of peak effect for each drug. Colorectal distention, as a noxious visceral stimulus, was applied to two groups while cardiovascular and visceromotor responses, respectively, were recorded. A third group received hot plate testing as a somatic nociceptive stimulus. Intrathecal morphine and lidocaine both attenuated the cardiovascular and visceromotor responses to colorectal distention and increased hot plate latencies in a dose- and time-dependent manner. With the use of isobolographic analysis, the coadministration of morphine and lidocaine demonstrated a synergistic, supraadditive interaction during visceral nociception (P less than 0.001) and somatic nociception (P less than 0.005). In a fourth group, motor function was evaluated by an inclined screen method. Intrathecal lidocaine in the dosage range tested during isobolographic analysis revealed no motor deficits. These data clearly demonstrate antinociceptive synergy between intrathecal morphine and lidocaine during visceral and somatic nociception at dosages that do not impair motor function.