Surgical pain attenuates acute morphine tolerance in rats

Nociceptive stimuli, such as formalin-induced pain and adjuvant-induced arthritis, attenuate tolerance to morphine antinociception. In this study, we have explored the effect of upper and lower abdominal surgical pain on the prevention of acute tolerance to morphine antinociception in Sprague-Dawley rats. Group I received lower abdominal surgery (LAS) and i.v. morphine infusion; group II received LAS and i.v. saline infusion; group III received upper abdominal surgery (UAS) and i.v. morphine infusion; group IV received UAS and i.v. saline infusion; group V received i.v. morphine infusion; and group VI received i.v. saline infusion. The antinociceptive effects of morphine were measured by an infrared thermal tail flick test. We also measured plasma concentrations of morphine in rats receiving morphine infusions with or without surgical treatment. We found that acute tolerance to morphine antinociception developed after 2 h following i.v. infusion of morphine alone. However, both UAS and LAS significantly slowed the rate of development of acute tolerance to morphine. The area under the time-response curves (AUC) of groups I and III were mean 34,556 (SD 5607) and 32,548 (9783), respectively, which were significantly different from that of group V (18,759 (8225)) (P < 0.01). Also, there were no significant differences between groups I and III. There were no significant differences between groups for plasma morphine concentrations during the 8-h study (e.g. groups I, III and V: 179.9 (22.6), 182.7 (14.4) and 170.9 (15.8) ng ml-1 at 8 h, respectively) and we suggest that the appearance of acute morphine tolerance after morphine infusion is not pharmacokinetic in nature.