Placebo and nocebo mechanisms can lead to clinically significant modulation of pain. Although learning is considered to be the broad mechanism underlying placebo analgesia as well as nocebo hyperalgesia, critical differences have emerged in their specific mechanisms. One of the most interesting of these is that whereas placebo analgesia seems to be relatively short-lived, nocebo hyperalgesia appears more resistant to extinction, often persisting indefinitely. The current study examined why nocebo hyperalgesia persists longer than placebo analgesia. Sixty healthy volunteers were randomized to receive placebo conditioning, nocebo conditioning, or no conditioning using an experimental pain model with surreptitious decreases (placebo group) and increases (nocebo group) in pain stimulation paired with sham treatment during training. Pain was then assessed in a test phase with and without the sham treatment at equal pain stimulation. The conditioning procedure successfully induced placebo analgesia as well as nocebo hyperalgesia in the relevant groups, with nocebo hyperalgesia outlasting placebo analgesia, confirming nocebo hyperalgesia's resistance to extinction. Most interestingly, nocebo treatment led to heightened anticipatory anxiety ratings and autonomic arousal. Further, autonomic arousal completely mediated the effect of nocebo versus placebo training on extinction, suggesting that heightened autonomic arousal may be an important mechanism in the persistence of nocebo hyperalgesia. PERSPECTIVE:Heightened anticipatory anxiety in the form of elevated autonomic arousal may explain why nocebo hyperalgesia persists relative to placebo analgesia. As such, interventions that reduce anticipatory anxiety could reduce the burden of persistent nocebo hyperalgesia.

译文

:安慰剂和诺西博的机制可能导致临床上明显的疼痛调节。尽管学习被认为是安慰剂镇痛和Nocebo痛觉过敏的广泛机制,但在其具体机制上却出现了严重的差异。其中最有趣的现象之一是,尽管安慰剂镇痛作用相对较短,但Nocebo痛觉过敏似乎对灭绝具有更强的抵抗力,常常无限期地持续下去。当前的研究探讨了为什么Nocebo痛觉过敏比安慰剂镇痛持续时间更长。 60名健康志愿者被随机分配接受安慰剂调理,nocebo调理或不进行调理,使用实验性疼痛模型,在训练过程中,疼痛刺激与假治疗相伴暗中减少(安慰剂组)和增加(nocebo组)。然后在相同疼痛刺激下,在有或没有假手术治疗的测试阶段中评估疼痛。调理程序成功地在相关组中诱导了安慰剂镇痛以及诺西博的痛觉过敏,诺西博的痛觉过敏超过了安慰剂的镇痛作用,证实了诺西博的痛觉过敏对绝种的抵抗力。最有趣的是,nocebo治疗导致了更高的预期焦虑等级和自主神经唤醒。此外,自主唤醒完全介导了Nocebo与安慰剂训练对绝种的影响,这表明增强的自主唤醒可能是Nocebo痛觉过敏持续存在的重要机制。
观点:以较高的自主神经觉醒形式引起的预期焦虑加剧可能解释了为什么Nocebo痛觉过敏相对于安慰剂镇痛持续存在。因此,减少预期焦虑的干预措施可以减轻持续的Nocebo痛觉过敏的负担。

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