Bloomfield Saul S, Mitchell Jeanette, Cissell Gail, Barden Tom P
Division of Clinical Pharmacology and Toxicology, Department of Internal Medicine, Cincinnati, OH 45267 U.S.A. Department of Obstetrics and Gynecology, University of Cincinnati, College of Medicine, Cincinnati, OH 45267 U.S.A.
Pain. 1986 Nov;27(2):171-179. doi: 10.1016/0304-3959(86)90208-3.
Post-partum uterine cramping and episiotomy pain are established, frequently used, clinical pain models for efficacy trials of investigational new analgesic agents. To determine the respective assay sensitivity of these two models in assessing relative efficacy, we reviewed data from 6 phase II, randomized, stratified, parallel, placebo-controlled, double-blind, single-dose studies involving hospitalized women with moderate or severe post-partum uterine cramping (332 patients) or episiotomy pain (434 patients). Using subjective reports as indices of response, patients rated pain intensity and relief at periodic interviews for 6-7 h. Post-partum uterine cramping showed excellent assay sensitivity for detecting differences among peripherally acting analgesics. In the same clinical trial this model could discriminate between a new drug and aspirin 650 mg, a standard reference analgesic, and between 2 graded doses of the new active agent (i.e., good upside sensitivity). In addition the uterine cramp model showed separation between placebo and all active agents (i.e., good downside sensitivity). Episiotomy pain demonstrated similar upside and downside discrimination in clinical trials of several weak centrally acting drugs. These data suggest that post-partum cramping is an excellent pain model for analgesic investigation of new non-steroidal anti-inflammatory drugs, and episiotomy pain for new weak narcotic and opioid analgesics.
产后子宫绞痛和会阴切开术疼痛是公认的、常用的临床疼痛模型，用于研究新型镇痛药的疗效试验。为了确定这两种模型在评估相对疗效方面各自的测定敏感性，我们回顾了6项II期随机、分层、平行、安慰剂对照、双盲、单剂量研究的数据，这些研究涉及患有中度或重度产后子宫绞痛的住院妇女（332例患者）或会阴切开术疼痛的住院妇女（434例患者）。以主观报告作为反应指标，患者在6 - 7小时的定期访谈中对疼痛强度和缓解情况进行评分。产后子宫绞痛在检测外周作用镇痛药之间的差异方面显示出极佳的测定敏感性。在同一临床试验中，该模型能够区分新药与650毫克阿司匹林（一种标准参考镇痛药），以及区分新药活性成分的2个分级剂量（即良好的上限敏感性）。此外，子宫绞痛模型显示出安慰剂与所有活性药物之间的区分（即良好的下限敏感性）。在几种弱中枢作用药物的临床试验中，会阴切开术疼痛表现出类似的上下限区分。这些数据表明，产后绞痛是新型非甾体抗炎药镇痛研究的极佳疼痛模型，而会阴切开术疼痛则是新型弱麻醉性和阿片类镇痛药的良好模型。
