A study of the analgesic interaction between intrathecal morphine and subcutaneous nalbuphine in the rat

Nalbuphine reverses opioid-induced respiratory depression, but the effect on analgesia is unclear. The analgesic interaction between subcutaneous (sc) nalbuphine and intrathecal morphine in conscious, male, Sprague-Dawley rats implanted with chronic intrathecal catheters was investigated. Nalbuphine (10 mg/kg) injected 30 min after intrathecal morphine (4 micrograms) significantly antagonized the effect of morphine in the tail flick test. The antagonism was rapid in onset and persisted beyond the experimental period of 240 min. The magnitude and the duration of the effect were comparable to that observed with sc naloxone (1 mg/kg). In contrast to the results in the tail flick test, nalbuphine enhanced the effect of intrathecal morphine in the noninflamed paw pressure test. Nalbuphine (10 mg/kg) alone had no effect on the time course of tail flick latency but significantly increased paw pressure threshold during the 15-90 min interval after sc injection. Nalbuphine (0.5 mg/kg, sc) alone had no antinociceptive effect in either pain test and did not antagonize the antinociceptive effect of intrathecal morphine (4 micrograms) in the tail flick test. However, sc nalbuphine (0.5 mg/kg), injected 30 min after intrathecal morphine (1.5 micrograms), significantly enhanced the effect of morphine in the paw pressure test compared with intrathecal morphine + sc saline-treated rats. The results indicate a complex analgesic interaction between intrathecal morphine and sc nalbuphine. The net analgesic effect during the interaction was determined by the following: 1) the doses of morphine and nalbuphine; 2) the time after nalbuphine administration; and 3) the nature of the nociceptive stimulus. At lower doses, sc nalbuphine appeared to potentiate the effect of intrathecal morphine in the noninflamed paw pressure test.