The periaqueductal gray and Bayesian integration in placebo analgesia.
The periaqueductal gray and Bayesian integration in placebo analgesia.
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DOI：
10.7554/elife.32930
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发表时间：
2018-03-20
期刊：
影响因子：
7.7
通讯作者：
Büchel C
中科院分区：
文献类型：
--
作者：
Grahl A;Onat S;Büchel C
在安慰剂痛觉减退研究中，治疗期望和经验的强度是关键组成部分。然而，期望的可靠性或精确性大多被忽视，尽管这可能是个体间差异的一个来源。在本研究中，我们采用了贝叶斯框架，自然地结合了期望值和精度。这假定期望（先验）与传入的伤害性信息（可能性）相结合，两者都通过其相对精确度进行加权，以形成疼痛感受和安慰剂效应。62名健康受试者在fMRI期间接受热痛。安慰剂效应在具有更精确治疗预期的受试者中更明显，并且与先前预期的相对精确度呈正相关。在导水管周围灰质和延髓头端腹内侧区观察到这种精确度的神经相关性，表明在脑干水平上，期望的精确度已经可以影响疼痛感知，这为安慰剂痛觉减退中的贝叶斯整合提供了强有力的证据。在第二次世界大战的一个战场上，外科医生亨利比彻的吗啡用完了。令他惊讶的是，他发现用盐水代替失踪的吗啡可以让他继续为受伤的士兵做手术。虽然盐水不含有效的止痛成分，但它减轻了士兵的疼痛。这是安慰剂效应的一个例子。安慰剂已被证明可以减少对疼痛的自主反应，如出汗。它们还调节处理疼痛的大脑区域的活动。但为什么我们中的一些人比其他人经历更大的安慰剂效应？Grahl等人提出，安慰剂效应的大小取决于我们对治疗的预期。更具体地说，这取决于这些期望有多精确。想象一下，两个人多次接受相同的治疗，并且经历了相同的平均疼痛减轻。但对于一个人来说，每次治疗减少的疼痛量大致相同。对于另一个人来说，这种治疗有时会大大减轻他们的痛苦，而其他时候几乎没有。第一个人会比第二个人对未来的治疗效果有更准确的预期。Grahl等人提出，第一个人将因此经历更大的安慰剂效应，以响应“假”版本的治疗。为了验证这个想法，Grahl等人对躺在大脑扫描仪中的健康志愿者的前臂施加了痛苦的热量。在一半的试验中，志愿者被告知他们还将接受电击止痛疗法。事实上，这种待遇从未被采用过。每次试验后，志愿者们都会对他们所经历的疼痛强度进行评分。正如预期的那样，当志愿者认为他们正在接受止痛治疗时，他们报告的疼痛减轻了。此外，那些对治疗有更精确期望的志愿者比那些不太精确期望的志愿者报告了更大的疼痛缓解。前一组的大脑主要疼痛处理中心之一，导水管周围灰质的活动也较少。这些发现有助于阐明为什么有些人比其他人经历更大的安慰剂效应。他们认为，通过向患者提供有关其可能有效性的精确信息，帮助患者形成对治疗的精确预期，可能会增强安慰剂效应。需要进一步的研究来确定这种现象是否也发生在疼痛障碍患者中。如果是这样的话，它可以帮助这些患者使用更少的活性止痛药来控制疼痛。
In placebo hypoalgesia research, the strength of treatment expectations and experiences are key components. However, the reliability or precision of expectations had been mostly ignored although being a likely source for interindividual differences. In the present study, we adopted a Bayesian framework, naturally combining expectation magnitudes and precisions. This postulates that expectations (prior) are integrated with incoming nociceptive information (likelihood) and both are weighted by their relative precision to form the pain percept and placebo effect. Sixty-two healthy subjects received heat pain during fMRI. Placebo effects were more pronounced in subjects with more precise treatment expectations and correlated positively with the relative precision of the prior expectation. Neural correlates of this precision were observed in the periaqueductal gray and the rostral ventromedial medulla, indicating that already at the level of the brainstem the precision of an expectation can influence pain perception presenting strong evidence for Bayesian integration in placebo hypoalgesia. On a battlefield in World War II, surgeon Henry Beecher ran out of morphine. To his surprise, he found that replacing the missing morphine with saltwater allowed him to continue operating on wounded soldiers. Although saltwater contains no active pain-relieving ingredients, it reduced the soldiers’ pain. This is an example of the placebo effect. Placebos have been shown to reduce autonomic responses to pain, such as sweating. They also modulate activity in brain regions that process pain. But why do some of us experience larger placebo effects than others? Grahl et al. propose that the size of the placebo effect depends on our expectations about a treatment. More specifically, it depends on how precise those expectations are. Imagine two people who have taken the same treatment many times, and who have experienced the same average reduction in pain. But for one person, the treatment reduced their pain by roughly the same amount each time. For the other, the treatment sometimes reduced their pain by a large amount and other times hardly at all. The first person will have more precise expectations than the second about how effective the treatment will be in future. Grahl et al. propose that the first person will thus experience a greater placebo effect in response to a ‘fake’ version of the treatment. To test this idea, Grahl et al. applied painful heat to the forearms of healthy volunteers lying inside a brain scanner. On half the trials, the volunteers were told that they would also receive an electrical pain-relieving therapy. In reality, this treatment was never applied. After each trial, the volunteers rated the intensity of the pain they had experienced. As expected, the volunteers reported less pain when they thought they were receiving a pain-relieving treatment. Moreover, those volunteers with more precise expectations about the treatment reported greater pain relief than volunteers with less precise expectations. The former group also showed less activity in one of the brain’s major pain-processing centers, the periaqueductal gray. These findings help shed light on why some people experience larger placebo effects than others. They suggest that helping patients form precise expectations about their treatment, by giving them precise information about its likely effectiveness, may boost the placebo effect. Further studies are needed to determine whether this phenomenon also occurs in patients with pain disorders. If it does, it could help such patients manage their pain using fewer active painkillers.