Long-Term Changes in the Antinociceptive Potency of Morphine or Dexmedetomidine After a Single Treatment

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In Brief Acute tolerance develops after a single administration of opiate or α2-adrenergic agonists, but the characteristics of the delayed type of acute tolerance have not been analyzed in acute and inflammatory thermal pain tests. We investigated the long-term changes in the antinociceptive potency of morphine (10 mg/kg) injected intraperitoneally and the α2-adrenoceptor agonist dexmedetomidine (150 μg/kg intraperitoneally) on acute heat pain (tail-flick test) sensitivity and on carrageenan-induced inflammatory thermal hyperalgesia (paw withdrawal test) after a second injection 7 days later. The first treatment did not influence the baseline values on Day 8 in either test. In the tail-flick test, the antinociceptive potency of morphine, but not that of dexmedetomidine, was significantly decreased after repeated administration, suggesting a delayed type of acute tolerance to morphine. In contrast, the antihyperalgesic effect of morphine in the paw withdrawal test did not change after repeated injection, whereas the potency of dexmedetomidine was increased on Day 8. There were significant differences between the inflamed and noninflamed sides on Day 1 but not on Day 8, revealing an increased potency of the drugs on the inflamed side. There was no sign of cross-tolerance between the two drugs in either pain test. These data indicate long-term changes in the antinociceptive potency of morphine or dexmedetomidine after single treatment in different heat pain tests. IMPLICATIONS: A delayed type of acute tolerance developed to morphine, but not to dexmedetomidine, on acute pain test. The antihyperalgesic effects of morphine were not changed on repeated administration one week later, whereas the potency of dexmedetomidine was increased. There was no sign of cross-tolerance between the two drugs.

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