Abstract：
While treatment side effects may adversely impact patients, they could also potentially function as indicators for effective treatment. In this study, we investigated whether and how side effects can trigger positive treatment expectations and enhance treatment outcomes. In this pre-registered trial (DRKS00026648), 77 healthy participants were made to believe that they will receive fentanyl nasal sprays before receiving thermal pain in a controlled experimental setting. However, nasal sprays did not contain fentanyl, rather they either contained capsaicin to induce a side effect (mild burning sensation) or saline (inert). After the first session, participants were randomized to two groups and underwent functional MRI. One group continued to believe that the nasal sprays could contain fentanyl while the other group was explicitly informed that no fentanyl was included. This allowed for the independent manipulation of the side effects and the expectation of pain relief. Our results revealed that nasal sprays with a side effect lead to lower pain than inert nasal sprays without side effects. The influence of side effects on pain was dependent on individual beliefs about how side effects are related to treatment outcome, as well as on expectations about received treatment. Functional MRI data indicated an involvement of the descending pain modulatory system including the anterior cingulate cortex and the periaqueductal gray during pain after experiencing a nasal spray with side effects. In summary, our data show that mild side effects can serve as a signal for effective treatment thereby influencing treatment expectations and outcomes, which is mediated by the descending pain modulatory system. Using these mechanisms in clinical practice could provide an efficient way to optimize treatment outcome. In addition, our results indicate an important confound in clinical trials, where a treatment (with potential side effects) is compared to placebo.
摘要：
虽然治疗副作用可能会对患者产生不利影响，它们也可能作为有效治疗的指标。在这项研究中,我们调查了副作用是否以及如何触发积极的治疗预期并提高治疗结局.在这个预先注册的审判(DRKS00026648)中，77名健康参与者相信他们将在受控实验环境中接受热痛之前接受芬太尼鼻喷雾剂。然而,鼻腔喷雾剂不含芬太尼,相反，它们含有辣椒素以引起副作用（轻度灼烧感）或盐水（惰性）。在第一次会议之后,参与者被随机分为两组,并接受功能磁共振成像(fMRI).一组继续认为鼻喷雾剂可能含有芬太尼，而另一组被明确告知不包括芬太尼。这允许对副作用的独立操纵和疼痛缓解的期望。我们的结果表明，有副作用的鼻喷雾剂比无副作用的惰性鼻喷雾剂疼痛更低。副作用对疼痛的影响取决于个体对副作用如何与治疗结果相关的信念。以及对接受治疗的期望。FMRI数据表明，在经历有副作用的鼻喷雾剂后，疼痛包括前扣带回皮质和导水管周围灰色在内的下降疼痛调节系统。总之,我们的数据表明，轻度副作用可以作为有效治疗的信号，从而影响治疗预期和结果，这是由下降的疼痛调节系统介导的。在临床实践中使用这些机制可以提供优化治疗结果的有效方法。此外,我们的结果表明临床试验中有一个重要的混淆，将治疗（具有潜在副作用）与安慰剂进行比较。
