Bloomfield S S, Barden T P, Mitchell J
Clin Pharmacol Ther. 1976 Oct;20(4):499-503. doi: 10.1002/cpt1976204499.
Aspirin and codeine, standard reference analgesics, are frequently used as positive controls in clinical trials of new oral analgesics. In randomized parallel double-blind studies, single doses of aspirin and codeine were compared with placebo in episiotomy pain (99 patients) and in postpartum uterine pain (130 patients), common models in analgesic trials. With aspirin, 600 and 1,200 mg, in episiotomy pain, analgesia as measured by pain intensity difference (PID) scores began within 1 hr, peaked at the second hour (p less than 0.01), and continued to the fifth hour (p less than 0.01). In uterine pain, responses with aspirin, 650 mg, were observed to be equally good. With codeine, 60 mg, in episiotomy pain measurable analgesia was present by the second hour and was significant at the fourth hour (p less than 0.05); in uterine pain, responses were indistinguishable from placebo throughout an 8-hr time-course. Codeine seemed ineffective and therefore umacceptable as a positive control in uterine pain. These data imply that the two postpartum pain models are qualitatively different: episiotomy pain seems sensitive to both aspirin and codeine, while uterine pain appears sensitive to aspirin but not to codeine.
阿司匹林和可待因这两种标准参考镇痛药,在新型口服镇痛药的临床试验中常被用作阳性对照。在随机平行双盲研究中,将单剂量的阿司匹林和可待因与安慰剂在会阴切开术疼痛(99例患者)和产后子宫疼痛(130例患者)中进行比较,这是镇痛试验中常用的模型。对于阿司匹林,600毫克和1200毫克剂量用于会阴切开术疼痛时,通过疼痛强度差值(PID)评分测量的镇痛效果在1小时内开始出现,在第2小时达到峰值(p<0.01),并持续到第5小时(p<0.01)。在子宫疼痛中,650毫克阿司匹林的效果同样良好。对于可待因,60毫克剂量用于会阴切开术疼痛时,可测量的镇痛效果在第2小时出现,在第4小时显著(p<0.05);在子宫疼痛中,在整个8小时的时间过程中,其效果与安慰剂无差异。可待因似乎无效,因此作为子宫疼痛的阳性对照是不可接受的。这些数据表明,两种产后疼痛模型在性质上有所不同:会阴切开术疼痛似乎对阿司匹林和可待因都敏感,而子宫疼痛似乎对阿司匹林敏感,但对可待因不敏感。