Department of Physiology and Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, Australia.
Eur J Pain. 2012 Aug;16(7):1005-13. doi: 10.1002/j.1532-2149.2011.00104.x. Epub 2012 Jan 19.
To determine whether there is a sex difference in placebo and ibuprofen analgesia expectancy.
We measured detection and tolerance thresholds for electrically induced pain in the ear lobe in healthy subjects (10 male, 10 female) to study sex differences in expectancy following either ibuprofen 800 mg or placebo in four different expectancy states. Subjects took ibuprofen or placebo in a two-by-two factorial design (the balanced placebo design). We randomly assigned subjects to start in one of the four expectancy states. We analysed the results using analysis of variance for repeated measures with baseline pain as a covariate.
We found no sex difference in baseline pain threshold or tolerance levels. When partitioned by sex and expectancy state, analgesia only occurred in males during positive expectancy states at 2, 3 and 4 h post-placebo, and at 1 and 2 h post-ibuprofen. The time course of analgesic action in males was as expected considering the pharmacokinetic profile of ibuprofen. Our study found that dosages of 800 mg of ibuprofen are ineffective in producing analgesia in women regardless of their expectations. We hypothesize that ibuprofen analgesia is produced by a combination of specific pharmacological effects and a non-specific beta endorphin-mediated placebo effect. Whatever the mechanism responsible for the analgesic response seen in males, this research re-emphasizes the importance of psychological factors in determining drug response. It also shows that these factors can differ between men and women, and thus the contribution of psychological factors on analgesia needs to be seriously re-evaluated.
确定安慰剂和布洛芬镇痛预期是否存在性别差异。
我们测量了健康受试者（10 名男性，10 名女性）耳叶电刺激引起的疼痛的感知和耐受阈值，以研究在四种不同的预期状态下，服用布洛芬 800mg 或安慰剂后，期望对性别差异的影响。采用二因素（平衡安慰剂设计）设计，受试者服用布洛芬或安慰剂。我们随机将受试者分配到四个预期状态中的一个开始。我们使用重复测量方差分析，以基线疼痛为协变量分析结果。
我们发现基线疼痛阈值或耐受水平没有性别差异。当按性别和预期状态划分时，只有在阳性预期状态下，即安慰剂后 2、3 和 4 小时以及布洛芬后 1 和 2 小时，男性才会出现镇痛作用。考虑到布洛芬的药代动力学特征，男性的镇痛作用时间过程符合预期。我们的研究发现，无论女性的期望如何，800mg 布洛芬的剂量都不能有效产生镇痛作用。我们假设布洛芬的镇痛作用是由特定的药理学作用和非特异性β内啡肽介导的安慰剂效应共同产生的。无论导致男性出现镇痛反应的机制是什么，这项研究都再次强调了心理因素在确定药物反应中的重要性。它还表明这些因素在男性和女性之间可能存在差异，因此需要认真重新评估心理因素对镇痛的贡献。
