Characterization of the antinociceptive effects of oxycodone in diabetic mice.
We investigated the antinociceptive efficacy of systemic and centrally injected oxycodone on thermal hyperalgesia in streptozotocin-induced diabetic mice. The antinociceptive response was assessed by recording the latency in the tail-flick test using the radiant heat from a 50-W projection bulb on the tail. The tail-flick latency in diabetic mice was significantly shorter than that in non-diabetic mice. Oral (p.o.) and i.t., but not i.c.v., administration of oxycodone prolonged the tail-flick latency in diabetic mice to a level that was considerably longer than the baseline latency in non-diabetic mice. However, morphine did not significantly inhibit the tail-flick response in diabetic mice. The antinociceptive effect of either p.o. or i.t. oxycodone in non-diabetic mice, but not in diabetic mice, was antagonized by pretreatment with a selective mu-opioid receptor antagonist, beta-funaltrexamine. In non-diabetic mice, pretreatment with a selective kappa-opioid receptor antagonist, nor-binaltorphimine, had no effect on the peak antinociceptive effect of either p.o. or i.t. oxycodone at 30 min after administration, however, it slightly but significantly reduced oxycodone-induced antinociception at 60 and 90 min after administration. On the other hand, pretreatment with nor-binaltorphimine practically abolished the antinociceptive effects of both p.o.- and i.t.-administered oxycodone in diabetic mice. Naltrindole, a selective delta-opioid receptor antagonist, had no effects on the antinociceptive effect of oxycodone in either non-diabetic or diabetic mice. These results suggest that the antinociceptive effects of oxycodone may be mediated by spinal kappa-opioid receptors in diabetic mice, whereas it may interact primarily with supraspinal and spinal mu-opioid receptors in non-diabetic mice.
Nozaki
Chihiro
C
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 4-41, Shinagawa-ku, Tokyo 142-8501, Japan.
Saitoh
Akiyoshi
A
Kamei
Junzo
J
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D051379:Mice; D008813:Mice, Inbred ICR; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D010098:Oxycodone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control*; D010147:Pain Measurement / Q000379:methods; D013311:Streptozocin
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; C051844:norbinaltorphimine; D009271:Naltrexone; D013311:Streptozocin; C024524:beta-funaltrexamine; D010098:Oxycodone