Different Placebos, Different Mechanisms, Different Outcomes: Lessons for Clinical Trials.
Different Placebos, Different Mechanisms, Different Outcomes: Lessons for Clinical Trials.
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DOI：
10.1371/journal.pone.0140967
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Dogue S
中科院分区：
文献类型：
--
作者：
Benedetti F;Dogue S
临床试验使用安慰剂是假设它们是惰性的，因此所有的安慰剂都被认为是相同的。在这里，我们表明这种假设是错误的，不同的安慰剂程序与不同的治疗仪式有关，而这些仪式反过来又触发不同的机制并产生不同的治疗结果。我们研究了高海拔或低气压缺氧引起的头痛，其中使用了两种不同的安慰剂。第一组是通过面罩吸入安慰剂氧气，第二组是安慰剂阿司匹林和药片一起吞下。这两种安慰剂都是在调节过程后给予的，即连续三次给予真正的氧气或真正的阿司匹林以减轻头痛。我们发现，在真正的氧气调节后，安慰剂氧诱导疼痛缓解，并减少通气，血液碱中毒和唾液前列腺素（PG）E2，但没有增加血氧饱和度（SO2）。相比之下，经过真正的阿司匹林调理后，安慰剂阿司匹林通过抑制环加氧酶的所有产物PGD2、PGE2、PGF2、PGI2、血栓素（TX）A2来缓解疼痛，而不影响通气和血液碱中毒。因此，两种不同的安慰剂，与两种不同的治疗方法相关联，使用两种不同的途径来减轻头痛。安慰剂吸氧后的镇痛效果优于安慰剂阿司匹林。这些发现表明，不同的安慰剂可能使用不同的机制来减少高原头痛，这取决于治疗仪式和给药途径。在临床试验中，为了不引起错误的解释，应该非常仔细地选择安慰剂和结果测量。
Clinical trials use placebos with the assumption that they are inert, thus all placebos are considered to be equal. Here we show that this assumption is wrong and that different placebo procedures are associated to different therapeutic rituals which, in turn, trigger different mechanisms and produce different therapeutic outcomes. We studied high altitude, or hypobaric hypoxia, headache, in which two different placebos were administered. The first was placebo oxygen inhaled through a mask, whereas the second was placebo aspirin swallowed with a pill. Both placebos were given after a conditioning procedure, whereby either real oxygen or real aspirin was administered for three consecutive sessions to reduce headache pain. We found that after real oxygen conditioning, placebo oxygen induced pain relief along with a reduction in ventilation, blood alkalosis and salivary prostaglandin (PG)E2, yet without any increase in blood oxygen saturation (SO2). By contrast, after real aspirin conditioning, placebo aspirin induced pain relief through the inhibition of all the products of cyclooxygenase, that is, PGD2, PGE2, PGF2, PGI2, thromboxane (TX)A2, without affecting ventilation and blood alkalosis. Therefore, two different placebos, associated to two different therapeutic rituals, used two different pathways to reduce headache pain. The analgesic effect following placebo oxygen was superior to placebo aspirin. These findings show that different placebos may use different mechanisms to reduce high altitude headache, depending on the therapeutic ritual and the route of administration. In clinical trials, placebos and outcome measures should be selected very carefully in order not to incur in wrong interpretations.