Low dose naloxone enhances buprenorphine in a tooth pulp antinociceptive assay

Low dose naloxone was reported to produce analgesia of long duration in patients who received buprenorphine. A rabbit tooth pulp antinociceptive model was utilized to evaluate a possible interaction of buprenorphine and naloxone. Naloxone (0.001 mg/kg i.v.) 210 min after buprenorphine (0.10 mg/kg i.v.) significantly increased the % MPE from 48 +/- 5% to 78 +/- 6%. This increased activity occurred within 90 min after naloxone injection and had a duration of 2 hr. Naloxone, 0.1 mg/kg, or saline 0.1 ml/kg did not increase nor reduce the buprenorphine antinociceptive effect. Naloxone alone (0.001 mg/kg) produced a peak antinociceptive effect of 43 +/- 14% MPE which was significantly greater than that of the saline control group. Using a graded dose response paradigm in the rabbit tooth pulp model, the graded dose response curve of buprenorphine was significantly shifted upwards after preadministration of 0.001 mg/kg naloxone. The slopes of both the ascending and descending limbs of the biphasic buprenorphine dose response curves were not significantly different. The peak % MPE achieved by buprenorphine in the presence of 0.001 mg/kg naloxone (62 +/- 8%) was significantly greater than the buprenorphine-saline control (23 +/- 4%). It appears that a low dose of naloxone produces antinociception which enhances that of buprenorphine.