环氧化酶-2抑制剂帕瑞昔布对吗啡镇痛耐受和吗啡诱导的大鼠痛觉过敏的抑制作用

The effects of cyclooxygenase-2 inhibitor parecoxib on morphine tolerance and morphine-induced hyperalgesia in rats

目的了解环氧化酶-2(COX-2)抑制剂帕瑞昔布在吗啡镇痛耐受与吗啡诱导的大鼠痛觉过敏上的作用。方法 (1)24只SD大鼠随机分为4组(n=6),分别腹腔内注射帕瑞昔布(5、10、20mg/kg)或等体积生理盐水,分别于药物注射前和注射后30、60min行压尾测试了解大鼠机械疼痛阈值并根据结果选择合适的亚镇痛剂量。(2)30只SD大鼠随机分为5组(n=6),各组分别皮下注射吗啡(10mg/kg)或等体积生理盐水,并于吗啡注射前15min腹腔内注射亚镇痛剂量帕瑞昔布(10mg/kg)或等体积生理盐水,连续给药14 d;其中3组分别于吗啡注射的全程14d(1～14d),前7d(1～7 d),后7 d(8～14d)注射帕瑞昔布。在每次给药前30 min和给药后60min分别对大鼠进行压尾测试,观察大鼠机械疼痛阈值改变。结果 (1)腹腔内注射帕瑞昔布5mg/kg和10mg/kg不会产生明显镇痛效应(P>0.05),可作为亚镇痛下剂量使用。(2)连续皮下注射吗啡可诱导大鼠产生机械痛觉过敏和吗啡镇痛耐受。(3)全程14d(1～14d)和前7d(1～7d)注射亚镇痛剂量帕瑞昔布可抑制吗啡诱导的痛觉过敏和吗啡镇痛耐受(P<0.01),而后7d(8～14d)注射帕瑞昔布则无明显抑制效果(P>0.05)。结论早期全程使用亚镇痛剂量的帕瑞昔布可抑制吗啡镇痛耐受与吗啡诱导的痛觉过敏。

Objective To investigate the effects of parecoxib on morphine tolerance and morphine induced hyperalgesia in rats. Methods （ 1 ） Twenty - four SD rats were randomly assigned into 4 groups （ n = 6）, in which intraperitoheal administration of parecoxib （5, 10 and 20 mg/kg） and placebo saline were given. Mechanical nociceptive thresholds were measured by the tail pressure test before and 30, 60 min after drug administration to determine the sub - analgesic doses. （ 2 ） Another 30 SD rats were randomly assigned into 5 groups （ n = 6 ）, in which subcutaneous administration of morphine （ 10 mg/kg） or saline once a day for 14 days were given, with additional intraperitoneal administration of parecoxib （ I0 mg,/kg） or saline was given 15 min before morphine injection. Adjuvant parecoxib were given for during the all 14 days, the first week or the last week in 3 of the 5 groups. Mechanical nociceptive thresholds were also assessed. Re- suits （ l ） Parecoxib at 5 or 10 mg/kg produced no antinociception, thus suggesting as sub - analgesic doses. （2） Re- peated subcutaneous administrations of morphine induced tolerance and mechanical hyperalgesia. （3） Administrations of parecoxib for the whole 2 weeks or the 1 st week inhibited morphine - induced tolerance and hyperalgesia. Conclusion Early administration of sub - analgesic parecoxib inhibits morphine tolerance and morphine - induced hyperalgesia in rats.