Winter L, Nadeson R, Tucker A P, Goodchild C S
Monash University Department of Anaesthesia, Monash Medical Centre, Clayton, Victoria, Australia.
Anesth Analg. 2003 Sep;97(3):798-805. doi: 10.1213/01.ANE.0000075835.73967.F3.
In this study, we investigated the antinociceptive and sedative effects of the opioids fentanyl, morphine, and oxycodone given alone and in combination with two neurosteroids: alphadolone and alphaxalone. An open-field activity monitor and rotarod apparatus were used to define the sedative effects caused by opioid and neurosteroid compounds given alone intraperitoneally to male Wistar rats. Dose-response curves for antinociception were constructed using only nonsedative doses of these drugs. At nonsedating doses, fentanyl, morphine, and oxycodone all caused dose-dependent tail flick latency (TFL) antinociceptive effects. Because neither neurosteroid altered TFL, electrical current was used as the test to determine doses of neurosteroid that caused antinociceptive effects at nonsedative doses. Alphadolone 10 mg/kg intraperitoneally caused significant antinociceptive effects in the electrical test but alphaxalone did not. All three opioid dose-response curves for TFL antinociception were shifted to the left by coadministration of alphadolone even though alphadolone alone had no effect on TFL. Alphaxalone given alone had no antinociceptive effects at nonsedative doses and it had no effect on opioid antinociception. Neither neurosteroid caused sedative effects when combined with opioids. We conclude that coadministration of alphadolone, but not alphaxalone, with morphine, fentanyl, or oxycodone potentiates antinociception and that this effect is not caused by an increase in sedation.
在本研究中，我们调查了阿片类药物芬太尼、吗啡和羟考酮单独使用以及与两种神经甾体：阿法多龙和阿法沙龙联合使用时的镇痛和镇静作用。使用旷场活动监测仪和转棒试验装置来确定单独腹腔注射给雄性Wistar大鼠的阿片类药物和神经甾体化合物所引起的镇静作用。仅使用这些药物的非镇静剂量构建镇痛的剂量-反应曲线。在非镇静剂量下，芬太尼、吗啡和羟考酮均引起剂量依赖性的甩尾潜伏期（TFL）镇痛作用。由于两种神经甾体均未改变TFL，因此用电刺激作为测试来确定在非镇静剂量下引起镇痛作用的神经甾体剂量。腹腔注射10mg/kg阿法多龙在电刺激试验中引起显著的镇痛作用，但阿法沙龙没有。尽管单独使用阿法多龙对TFL没有影响，但三种阿片类药物的TFL镇痛剂量-反应曲线在与阿法多龙联合给药时均向左移动。单独给予阿法沙龙在非镇静剂量下没有镇痛作用，并且对阿片类药物的镇痛作用没有影响。两种神经甾体与阿片类药物联合使用时均未引起镇静作用。我们得出结论，阿法多龙而非阿法沙龙与吗啡、芬太尼或羟考酮联合给药可增强镇痛作用，并且这种作用不是由镇静作用增强引起的。
