The opposite effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia
The opposite effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia
复制标题
DOI：
10.1016/0304-3959(95)00179-4
复制
发表时间：
1996-03-01
期刊：
影响因子：
7.4
通讯作者：
Benedetti, F
中科院分区：
文献类型：
--
作者：
Benedetti, F
内源性阿片类药物参与安慰剂镇痛的发现是理解安慰剂反应机制的重要一步。在本研究中，我们研究了阿片类药物拮抗剂纳洛酮和胆囊收缩素拮抗剂丙谷胺对实验诱导的缺血性疼痛的人类模型的安慰剂镇痛的影响。首先，我们发现部分安慰剂反应被纳洛酮逆转，证实了先前关于阿片类药物在安慰剂现象中作用的研究。其次，由于已证明丙谷胺可增强外源性和内源性阿片类药物的作用，我们分析了这种胆囊收缩素拮抗剂对安慰剂反应的影响，发现它可增强安慰剂镇痛作用。因此，安慰剂效应可以在两个相反的方向上调节：它可以被纳洛酮部分消除，并被丙谷胺增强。丙谷胺的安慰剂增强作用仅发生在安慰剂应答者中，而非无应答者中，这一事实表明内源性阿片系统的激活是丙谷胺作用的必要条件。这些结果表明胆囊收缩素在安慰剂反应中具有抑制作用，尽管丙谷胺对胆囊收缩素受体的低亲和力并不排除其他机制的可能性。
Discovery of the involvement of endogenous opiates in placebo analgesia represents an important step in understanding the mechanisms underlying placebo response. In the present study, we investigated the effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia in a human model of experimentally induced ischemic pain. First, we found that part of the placebo response was reversed by naloxone, confirming previous studies on the role of opioids in the placebo phenomenon. Second, since it was demonstrated that the action of exogenous and endogenous opiates is potentiated by proglumide,,we analysed the effects of this cholecystokinin antagonist on placebo response and found that it enhanced placebo analgesia. The placebo effect can thus be modulated in two opposite directions: it can be partially abolished by naloxone and potentiated by proglumide. The fact that placebo potentiation by proglumide occurred only in placebo responders, but not in non-responders, suggests that activation of an endogenous opiate system is a necessary condition for the action of proglumide. These results suggest an inhibitory role for cholecystokinin in placebo response, although the low affinity of proglumide for cholecystokinin receptors does not rule out the possibility of other mechanisms.