BACKGROUND & AIMS: BACKGROUND:A significant response to placebo in randomized controlled trials of treatments for cancer-related fatigue (CRF) had been reported. A retrospective study was conducted to determine the frequency and predictors of response to placebo effect and nocebo effects in patients with CRF treated in those trials. METHODS:The records of 105 patients who received placebo in 2 previous randomized clinical trials conducted by this group were reviewed. The proportion of patients who demonstrated clinical response to fatigue, defined as an increase in Functional Assessment of Chronic Illness Therapy-Fatigue score of > or = 7 from baseline to Day 8, and the proportion of patients with a nocebo effect, defined as those reporting >2 side effects, were determined. Baseline patient characteristics and symptoms recorded using the Edmonton Symptom Assessment Scale (ESAS) were analyzed to determine their association with placebo and nocebo effects. RESULTS:Fifty-nine (56%) patients had a placebo response. Worse baseline anxiety and well-being subscale score (univariate) and well-being (multivariate) were significantly associated with placebo response. Commonly reported side effects were insomnia (79%), anorexia (53%), nausea (38%), and restlessness (34%). Multivariate analysis indicated that worse baseline (ESAS) sleep, appetite, and nausea were associated with increased reporting of the corresponding side effects. CONCLUSIONS:Greater than half of advanced cancer patients enrolled in CRF trials had a placebo response. Worse baseline physical well-being score was associated with placebo response. Patients experiencing specific symptoms at baseline were more likely to report these as side effects of the medication. These findings should be considered in the design of future CRF trials.

背景与目标： 背景：在癌症相关疲劳（CRF）治疗的随机对照试验中，已报告对安慰剂有显着反应。进行了一项回顾性研究，以确定在那些试验中治疗的CRF患者中，对安慰剂作用和Nocebo作用的反应频率和预测因素。
方法：回顾了该组先前2项随机临床试验中105例接受安慰剂的患者的记录。表现出对疲劳有临床反应的患者比例（定义为从基线到第8天，慢性疾病治疗-疲劳功能评估的评分增加>或= 7）和具有Nocebo效果的患者比例（定义为报告确定了> 2种副作用。分析使用埃德蒙顿症状评估量表（ESAS）记录的基线患者特征和症状，以确定其与安慰剂和Nocebo效果的关联。
结果：五十九（56％）例患者发生了安慰剂反应。较差的基线焦虑和幸福感量表得分（单变量）和幸福感（多变量）与安慰剂反应显着相关。常见的副作用是失眠（79％），厌食（53％），恶心（38％）和躁动不安（34％）。多因素分析表明，基线（ESAS）睡眠，食欲和恶心变差与相应副作用的报告增多有关。
结论：参加CRF试验的晚期癌症患者中，有一半以上具有安慰剂反应。较差的基线身体健康评分与安慰剂反应相关。在基线时出现特定症状的患者更有可能将这些症状报告为药物的副作用。在将来的CRF试验设计中应考虑这些发现。

BACKGROUND & AIMS: INTRODUCTION:Although statins have a satisfactory safety profile and are well tolerated, many statin-treated patients report muscle symptoms in clinical practice which contribute to drug discontinuation and, consequently, adverse cardiovascular outcomes. AREAS COVERED:This narrative review will cover the definition and prevalence of statin intolerance, the clinical spectrum of statin-associated muscle symptoms (SAMS) with special focus on patients with only mild myalgias, the complexity of statin muscle intolerance diagnosis and provide an overview on the nocebo effect of particular importance for physicians. EXPERT OPINION:Many patients are unable to tolerate statin therapy, with SAMS being the most common cause of statin intolerance. The reported incidence of SAMS was consistently lower in randomized placebo-controlled trials than in observational studies. These results strongly suggested that SAMS were not always due to by the pharmacologic effects of statin therapy. Convincing patients that their muscle symptoms might be due to causes other than statin treatment is sometimes difficult. Furthermore, clinicians should not prematurely discontinue statin therapy before considering other possible causes, including the nocebo effect.

背景与目标： 简介：尽管他汀类药物具有令人满意的安全性且耐受性良好，但许多接受他汀类药物治疗的患者在临床实践中均报告有肌肉症状，这可能导致停药并因此导致不良的心血管结局。
覆盖的领域：本篇叙述性综述将涵盖他汀类药物不耐受的定义和患病率，他汀类药物相关的肌肉症状（SAMS）的临床范围，特别侧重于轻度肌痛的患者，他汀类药物肌肉耐受性诊断的复杂性，并概述Nocebo效应对医师尤为重要。
专家意见：许多患者无法耐受他汀类药物的治疗，其中SAMS是他汀类药物不耐受的最常见原因。在随机安慰剂对照试验中，SAMS的报道发病率始终低于观察性研究。这些结果强烈表明，SAMS并非总是由于他汀类药物疗法的药理作用所致。有时很难说服患者其肌肉症状可能是他汀类药物治疗以外的原因引起的。此外，临床医生在考虑其他可能的原因（包括Nocebo效应）之前，不应过早停用他汀类药物治疗。

BACKGROUND & AIMS: :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.

背景与目标： ：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。

BACKGROUND & AIMS: :Nocebo refers to adverse events (AEs) related to negative expectations that medical treatment will likely harm instead of heal and can be assessed in placebo-controlled randomized clinical trials (RCTs). We sought to examine the AEs following placebo administration in RCTs for depression (D). After a systematic Medline search for RCTs in depression published in the last decade we assessed percentages of placebo-treated patients reporting at least one AE or discontinuing due to placebo intolerance and searched for factors influencing nocebo's extent. Data were extracted from 21 RCTs fulfilling search criteria. Of 3255 placebo-treated patients, 44.7% (95% CI: 22.3-68.3%) reported at least one AE, and 4.5% (95% CI: 3.4-5.8%) discontinued placebo treatment due to intolerance. AE rates in placebo and active drug treated patients were correlated quantitatively (r=0.915, p<0.001) and qualitatively, but not dropout rates (r=0.047). We conclude that almost one out of 20 placebo treated patients discontinued treatment due to AEs, indicating a significant nocebo in trials for depression treatment adversely affecting adherence and efficacy of current treatments in clinical practice, with additional implications for trial designing.

背景与目标： ：Nocebo是指与不良预期有关的不良事件（AEs），不良预期是药物治疗可能会损害而不是治愈，可以在安慰剂对照的随机临床试验（RCT）中进行评估。我们试图检查在RCT中使用安慰剂治疗抑郁症后的不良事件（D）。在最近十年发表的针对抑郁症的RCT的系统化Medline搜索后，我们评估了接受至少一种AE或由于安慰剂不耐受而中断的安慰剂治疗患者的百分比，并搜索了影响nocebo程度的因素。从符合搜索标准的21个RCT中提取数据。在3255名接受安慰剂治疗的患者中，有44.7％（95％CI：22.3-68.3％）报告了至少一种AE，并且有4.5％（95％CI：3.4-5.8％）因不耐受而中断了安慰剂治疗。安慰剂组和活性药物治疗组的AE率在数量上相关（r = 0.915，p <0.001）和定性相关，但与辍学率无关（r = 0.047）。我们得出的结论是，在接受安慰剂治疗的20名患者中，几乎有1名因AE而终止治疗，这表明抑郁症治疗试验中的显着Nocebo不利地影响了当前治疗方法在临床实践中的依从性和疗效，并对试验设计产生了其他影响。

BACKGROUND & AIMS: :Aspect quite valued in the medical systems of all of the times, the doctor-patient relationship assumed secondary importance in the current biomedical model, depriving the modern therapeutic arsenal of a psyconeurophisiological intervention capable to complement the resolution of many organic disturbances. With the intention of rescuing this and other benefits, countless proposed by the humanization of the medicine have been appearing in the several sections of the health, remaining to scientific thought accept that this subjective relational increment can increase the effectiveness of the conventional treatments. Working as sensitization element, the recent experimental studies illustrate the possible benefits or harms that a doctor-patient relationship more or less humanized can provoke in the evolution of the diseases. Uniting the theories of classical conditioning and conscious expectation, the researches suggest that the doctor's posture, permeated by positive or negative manifestations (comments, suggestions, attitudes etc.), it can exercise similar influences in the patients' psyche, unchaining favorable or unfavorable neurophysiologic answers, acting as therapeutic or iatrogenic instrument, respectively.

背景与目标： ：在所有时代的医疗系统中都颇受重视的方面，医患关系在当前的生物医学模型中具有次要的重要性，这使现代治疗武库无法进行能够弥补许多有机物紊乱的精神上的精神病学干预措施。为了挽救这种益处和其他益处，医学的人性化提出了无数的建议，出现在健康的几个方面，但仍有科学思想认为，这种主观的关系增加可以提高常规治疗的有效性。作为敏化成分，最近的实验研究表明，或多或少人性化的医患关系可能会在疾病的发展中引发潜在的利弊。研究结合经典调节和有意识的期望的理论，认为医生的姿势被正或负的表现（评论，建议，态度等）所渗透，可以对患者的心理产生类似的影响，释放出有利或不利的神经生理学答案，分别作为治疗或医源性工具。

BACKGROUND & AIMS: BACKGROUND:The nocebo effect, when a harmless substance creates harmful effects in a person who takes it, is a clinically salient yet seldom studied phenomenon that may be associated with poorer treatment outcomes, perceived adverse events, and treatment discontinuation. The covert presence of nocebo responders in clinical trials may contribute to outcome variance in both placebo and active treatment arms for important primary and secondary endpoints. Nocebo effects are thought to be driven by expectancy and conditioning. METHOD:This study analyzed pooled clinical trial data in the placebo arms of controlled trials of antidepressant medications to investigate variables associated with the emergence of adverse outcomes in placebo-treated participants (N = 2,457). Specifically, we examined treatment-emergent adverse events (TEAEs) and discontinuation in placebo-treated individuals. Trials were commenced between 1993 and 2010 as studies of duloxetine versus active comparator and/or placebo. RESULTS:TEAEs were reported by 1,569 placebo-treated participants (63.9%), with 115 (4.7%) discontinuing from the studies due to TEAEs and 274 (11.2%) showing worsening of Hamilton Depression Rating Scale total score during placebo treatment. There was specifically no evidence to support the expectancy hypothesis, that reported TEAEs were influenced by adverse effects described in the clinical trials participant information and consent forms, or the conditioning hypothesis, that reported TEAEs would be influenced by adverse effect profiles of previous antidepressant medications used by these study participants. There was some evidence to suggest that people who had previously used complementary medications were more likely to report TEAEs. Variables specific to individual studies were the strongest predictors of TEAEs. DISCUSSION:In this study, TEAEs were very common among placebo-treated clinical trial participants. Unexpectedly, there was no evidence to associate TEAEs with adverse clinical outcomes, nor were the conditioning or expectancy hypotheses supported by these data. CONCLUSIONS:The nocebo effect is a common, covert, and poorly understood driver of clinical outcomes that requires further investigation.

背景与目标： 背景：nocebo效应在无害物质对服用者产生有害影响时，是一种临床上显着但很少研究的现象，可能与较差的治疗结果，可察觉的不良事件和停药有关。在临床试验中，隐秘的诺西波应答者的存在可能会导致安慰剂和积极治疗组中重要的主要终点和次要终点的预后差异。 Nocebo效应被认为是由期望和条件决定的。
方法：本研究分析了抗抑郁药物对照试验的安慰剂组中的汇总临床试验数据，以调查与安慰剂治疗的受试者不良结果出现相关的变量（N = 2,457）。具体而言，我们检查了治疗紧急不良事件（TEAE）和安慰剂治疗个体的停用情况。从1993年至2010年开始进行度洛西汀与活性比较剂和/或安慰剂的研究。
结果：1,569名接受安慰剂治疗的参与者报告了TEAE（63.9％），其中有115名（4.7％）由于TEAE退出研究，而有274名（11.2％）表明在安慰剂治疗期间汉密尔顿抑郁量表总分恶化。具体而言，没有证据支持预期假说，即报告的TEAE受临床试验参与者信息和同意书中描述的不良反应影响，或条件假说，报告的TEAE受先前使用的抗抑郁药的不良反应影响这些研究参与者。有证据表明，以前使用辅助药物的人更有可能报告TEAE。特定于研究的变量是TEAE的最强预测因子。
讨论：在这项研究中，TEAE在安慰剂治疗的临床试验参与者中非常普遍。出乎意料的是，没有证据表明TEAE与不良的临床结果相关联，这些数据也没有支持条件或预期假设。
结论：Nocebo效应是常见的，隐秘的，了解甚少的临床结果驱动因素，需要进一步研究。

BACKGROUND & AIMS: :Medical outcomes are strongly affected by placebo and nocebo effects. Prediction of who responds to such expectation effects has proven to be challenging. Most recent approaches to prediction have focused on placebo effects in the context of previous treatment experiences and expectancies, or personality traits. However, a recent model has suggested that basic somatosensory characteristics play an important role in expectation responses. Consequently, this study investigated not only the role of psychological variables, but also of basic somatosensory characteristics. In this study, 624 participants underwent a placebo and nocebo heat pain paradigm. Additionally, individual psychological and somatosensory characteristics were assessed. While no associations were identified for placebo responses, nocebo responses were associated with personality traits (e.g. neuroticism) and somatosensory characteristics (e.g. thermal pain threshold). Importantly, the associations between somatosensory characteristics and nocebo responses were among the strongest. This study shows that apart from personality traits, basic somatosensory characteristics play an important role in individual nocebo responses, in agreement with the novel idea that nocebo responses result from the integration of top-down expectation and bottom-up sensory information.

背景与目标： ：安慰剂和Nocebo的作用会严重影响医疗结局。预测谁对这种期望效应做出响应已被证明具有挑战性。最新的预测方法已将安慰剂的作用集中在先前的治疗经验和预期或人格特质的背景下。但是，最近的模型表明，基本的体感特征在预期反应中起着重要的作用。因此，本研究不仅研究了心理变量的作用，还研究了基本的体感特征。在这项研究中，624名参与者接受了安慰剂和Nocebo热痛范例。另外，评估了个体的心理和体感特征。虽然没有发现安慰剂反应的相关性，但nocebo反应与人格特质（例如神经质）和体感特征（例如热痛阈值）相关。重要的是，体感特征与Nocebo反应之间的关联最强。这项研究表明，除了人格特征外，基本的体感特征在个体nocebo反应中也起着重要作用，这与nocebo反应是由上而下的期望和自下而上的感官信息的整合所产生的新思想相一致。

BACKGROUND & AIMS: Experimental challenge studies may generate and test hypotheses regarding the pathophysiology of panic disorder and may serve to identify pathophysiologically relevant subtypes. It has been suggested that gender-related differences may be relevant in the development and maintenance of panic disorder. In a randomized double blind design the effects of placebo and sodium lactate administration in 14 female and 16 male patients with panic disorder and 23 healthy control subjects were compared using the Acute Panic Inventory (API) score and derived formal criteria for a panic attack. Panic attack frequency following sodium lactate was 76.6% in the patient group. Although control subjects had a lactate-induced increase in the API score as well, this effect was much weaker. No panic attacks occurred in patients with panic disorder or healthy control subjects receiving a placebo. However, a gender effect was observed in the putative panicogenic placebo conditionfemale patients with panic disorder had more subthreshold panic anxiety as measured with the API score. The data give evidence for an increased nocebo response in female patients with panic disorder.

背景与目标： 实验性挑战研究可能会生成和检验有关惊恐症病理生理的假设，并可能有助于识别与病理生理相关的亚型。已经提出，与性别相关的差异可能与恐慌症的发生和维持有关。在随机双盲设计中，使用急性恐慌量表（API）得分比较了惊慌发作的正式标准，比较了安慰剂和乳酸钠对14名女性和16名男性惊恐症患者和23名健康对照受试者的影响。在患者组中，乳酸钠后的惊恐发作频率为76.6％。尽管对照组也有乳酸诱导的API评分增加，但这种作用要弱得多。患有惊恐症的患者或接受安慰剂的健康对照受试者未发生惊恐发作。但是，在推定的恐慌性安慰剂病情中观察到性别效应，用API评分测得的女性惊恐症患者的亚阈值惊恐焦虑更高。数据为女性恐慌症患者的Nocebo反应增加提供了证据。

BACKGROUND & AIMS: BACKGROUND:A number of people are reporting an environmental sensitivity to sub-audible windfarm sound (infrasound), characterised by the experience of recurrent non-specific symptoms. A causal link between exposure and symptoms is not indicated by empirical evidence. Research indicates symptoms may be explained by the nocebo response, whereby health concerns and negative expectations, created from social discourse and media reports, trigger symptom reporting. OBJECTIVE:The experimental aim was to test whether providing a nocebo explanation for symptoms, to individuals reporting symptomatic experiences during infrasound exposure, would ameliorate symptoms during further exposure. METHOD:Sixty-six volunteers were randomly assigned to nocebo explanation or biological explanation groups. Participants were concurrently exposed to infrasound and audible windfarm sound, while reporting on current symptoms and mood, during two exposure sessions. Preceding session one, participants watched a presentation integrating media warnings about purported health risks posed by windfarm infrasound. Before session two, nocebo explanation participants viewed material outlining how nocebo responding could explain symptom reporting. Instead biological explanation participants watched material presenting pathophysiological theories for symptoms. RESULTS:During session one, participants reported increased symptoms and mood deterioration from baseline assessment. During session two symptom reporting and mood deterioration was maintained by biological explanation participants, while mood and symptoms reported by nocebo explanation participants returned to baseline levels. CONCLUSION:Results indicate that providing an explanation of the nocebo response, followed by exposure to infrasound, has the potential to operate as an intervention to reduce symptomatic experiences in people reporting symptoms attributed to windfarm generated infrasound.

背景与目标： 背景：许多人报告对可闻风电场声音（次声）具有环境敏感性，其特征是反复出现非特异性症状。经验证据并未表明暴露与症状之间的因果关系。研究表明，症状可能是由nocebo反应引起的，据此，社交讨论和媒体报道引起的健康担忧和负面期望触发了症状报告。
目的：实验目的是测试向次声暴露过程中有症状经历的人提供症状的nocebo解释是否会缓解进一步暴露过程中的症状。
方法：将66名志愿者随机分为nocebo解释组或生物学解释组。在两次暴露会议中，参与者在报告当前症状和情绪的同时，暴露于次声和可听到的风电场声音中。在第一节之前，参与者观看了一个演示，该演示结合了有关风电场次声带来的所谓健康风险的媒体警告。在第二部分之前，nocebo解释参与者查看了概述nocebo响应如何解释症状报告的材料。取而代之的是，生物学解释参与者观看了呈现病理生理学原理的症状材料。
结果：在第一节课中，参与者报告了基线评估后症状和情绪恶化的情况增加。在会议期间，生物学解释参与者保持了两种症状报告和情绪恶化，而nocebo解释参与者报告的情绪和症状恢复了基线水平。
结论：结果表明，对nocebo反应进行解释，然后再暴露于次声中，有可能作为一种干预措施来减少报告因风电场产生的次声所致症状的人的症状体验。

BACKGROUND & AIMS: BACKGROUND:In experimental placebo and nocebo studies, neutral control treatments are often administered for comparison with active treatments, but are of little interest, as, on average, they result in little change. Yet, when considered at an individual level, they fluctuate between baseline and subsequent measurements and may reveal important information about participants' placebo/nocebo responding tendencies.

METHODS:In a paradigm involving application of creams paired with positive, negative and neutral expectations, some subjects rated identical stimuli in the neutral condition as more painful while others as less painful after treatment with inert cream. We divided subjects into two groups based on the median split in these pre-post responses in the neutral control condition, and investigated (a) fMRI signal differences (post minus pre) between the two groups in neutral condition, and (b) seed-based resting state connectivity of the bilateral amygdala, known to be involved in emotional self-regulation, as well as ambiguous stimulus processing and aversive learning.

RESULTS:The results suggested that subjects who rated the same pain stimuli after treatment with explicitly neutral cream as more painful showed stronger fMRI activation of the amygdala during the experiment and had higher connectivity between the left amygdala and the striatum at rest. Neutral pre-post changes predicted behavioural placebo/nocebo response in this and two independent datasets.

CONCLUSION:These findings suggest that measuring pre-post change in the neutral control condition might provide important information about subjects' individual differences in placebo/nocebo response.

SIGNIFICANCE:Pre-post changes in pain ratings in neutral conditions are modulated by amygdala activity and connectivity and can be used to predict placebo/nocebo responses.

背景与目标： 背景：在实验性安慰剂和Nocebo研究中，通常将中性对照治疗与主动治疗进行比较，但兴趣不大，因为平均而言，它们的变化很小。但是，以个人水平考虑时，它们会在基线和后续测量之间波动，并可能揭示有关参与者安慰剂/ Nocebo反应趋势的重要信息。

方法：在涉及应用的范例中在对乳膏剂进行正面，负面和中性的期望配对后，有些受试者在惰性霜剂治疗后，在中性状态下对相同的刺激物评价为较痛苦，而另一些受试者对疼痛的评价则较小。我们根据中性对照条件下这些前后反应的中位数划分将受试者分为两组，并研究了（a）中性条件下两组之间的fMRI信号差异（减去前后），以及（b）基于双侧杏仁核的静息状态连通性，已知其参与情绪自我调节以及模棱两可的刺激处理和厌恶性学习。

结果：结果表明，在实验中，使用显着中性乳膏治疗的患者对相同的疼痛刺激评分更高，因为在实验过程中，更痛苦的显示杏仁核的功能磁共振成像激活更强，并且左侧杏仁核和静息纹状体之间的连通性更高。中性事前变化预测该行为和两个独立数据集中的行为安慰剂/ nocebo反应。

结论：这些发现表明，在中性对照条件下测量事前变化可提供重要的信息。有关受试者在安慰剂/ nocebo反应中个体差异的信息。

显着性：杏仁核的活动性和连通性可调节中性条件下疼痛等级的事前变化。安慰剂/ nocebo反应。