环氧化酶-2抑制剂帕瑞昔布对急性芬太尼诱导的大鼠痛觉过敏的抑制作用

The Inhibitant Effects Of Parecoxib, A Cyclooxygenase-2 Inhibitor, in Acute Fentanyl Induced Hyperalgesia in Rats

目的：了解不同剂量和给药时间点下环氧化酶－2抑制剂帕瑞昔布对急性芬太尼诱导的大鼠机械痛觉过敏的作用。方法：（1）30只SD大鼠随机分为5组（n ＝6）：生理盐水组、芬太尼组、芬太尼对照组、帕瑞昔布低剂量组和高剂量组，分别于皮下注射芬太尼或生理盐水，并在之前15 min腹腔内注射生理盐水或帕瑞昔布5或10 mg／kg，在芬太尼注射前、注射后第1～4小时每小时和第1～5天每天进行压尾测试了解机械疼痛阈值。（2）24只SD大鼠随机分为4组（n ＝6）：芬太尼组、帕瑞昔布－15 min组、帕瑞昔布4 h组和帕瑞昔布d1组，在不同时间点腹腔内注射帕瑞昔布10 mg／kg，压尾测试同上。结果：（1）皮下注射芬太尼可诱导大鼠机械痛觉过敏；腹腔内注射帕瑞昔布可抑制芬太尼诱导的机械痛敏，且高剂量比低剂量的抑制作用更明显。（2）痛觉过敏形成前腹腔内注射帕瑞昔布可抑制芬太尼诱导的机械痛敏，而形成后注射帕瑞昔布无明显作用。结论：早期给予亚镇痛剂量的帕瑞昔布可抑制芬太尼诱导的大鼠机械痛敏。

Objective To investigate the inhibitant effects of parecoxib, a cyclooxygenase-2 （COX-2） inhibitor, in acute fentanyl induced hyperalgesia in rats. Methods （1） Thirty SD rats （n=6 for each group） were subcutaneously injected with fentanyl （40 μg/kg × 4 times with a 15 min-interval） or saline to establish acute fentanyl induced hyperalgesia model, andparecoxib （5, 10 mg/kg） was administrated intraperitoneally in parecoxib group. Mechanical nociceptive thresholds were measured by the tail pressure test every hour during 1~4 hours and once a day during 1~5 days. （2） 24 SD rats （n = 6 foreach group） were subcutaneously injected with fentanyl as above described and randomly administrated intraperitoneally with parecoxib in 10 mg/kg in 15 min before and at the 4th hour and the 1st day after fentanyl injection except rats in the control group, mechanical nociceptive thresholds were measured by the tail pressure test at time points as above described. Results （1）Acute high dose fentanyl injection induced mechanical hyperalgesia and parecoxib （at 5 or 10 mg/kg）inhibited fentanyl induced hyperalgesia in rats. （2）Parecoxib inhibited fentanyl induced hyperalgesia at 15 min before and at the 4th hour after, but not on the 1st day after fentanyl injection. Conclusions This study provides the first evidence that subanalgesia doses of parecoxib had inhibitory effects on acute fentanyl induced hyperalgesia in time-dependent manners in rats.