Dept of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Dept of Health Sciences, VU University Amsterdam, Amsterdam, The Netherlands.
Eur Respir J. 2021 Sep 23;58(3). doi: 10.1183/13993003.03008-2020. Print 2021 Sep.
Cues such as odours that do not evoke bronchoconstriction can become triggers of asthma exacerbations. Despite its clinical significance, the neural basis of this respiratory nocebo effect is unknown.We investigated this effect in a functional magnetic resonance imaging (fMRI) study involving 36 healthy volunteers. The experiment consisted of an experience phase in which volunteers experienced dyspnoea while being exposed to an odorous gas ("Histarinol"). Volunteers were told that Histarinol induces dyspnoea by bronchoconstriction. This was compared with another odorous gas which did not evoke dyspnoea. Dyspnoea was actually induced by a concealed, resistive load inserted into the breathing system. In a second, expectation phase, Histarinol and the control gas were both followed by an identical, very mild load. Respiration parameters were continuously recorded and participants rated dyspnoea intensity after each trial.Dyspnoea ratings were significantly higher in Histarinol compared with control conditions, both in the experience and in the expectation phase, despite identical physical resistance in the expectation phase. Insula fMRI signal matched the actual load, a significant difference between Histarinol and control in the experience phase, but no difference in the expectation phase. The periaqueductal gray showed a significantly higher fMRI signal during the expectation of dyspnoea. Finally, Histarinol-related deactivations during the expectation phase in the rostral anterior cingulate cortex mirrored similar responses for nocebo effects in pain.These findings highlight the neural basis of expectation effects associated with dyspnoea, which has important consequences for our understanding of the perception of respiratory symptoms.
虽然这种呼吸类安慰剂效应具有重要的临床意义，但它的神经基础尚不清楚。在一项涉及 36 名健康志愿者的功能性磁共振成像（fMRI）研究中，我们对此效应进行了研究。该实验包含体验阶段和预期阶段。在体验阶段，志愿者在吸入一种有气味的气体（Histarinol）时会感到呼吸困难，同时被告知 Histarinol 会通过支气管收缩引起呼吸困难。将这种情况与另一种不会引起呼吸困难的有气味气体进行了对比。实际上，呼吸困难是通过隐藏在呼吸系统中的电阻负载引起的。在第二个预期阶段，Histarinol 和对照气体后都紧接着施加相同的、非常轻微的负载。呼吸参数连续记录，参与者在每次试验后对呼吸困难强度进行评分。尽管在预期阶段的物理阻力相同，但 Histarinol 组的呼吸困难评分明显高于对照条件，无论是在体验阶段还是在预期阶段。在体验阶段，岛叶 fMRI 信号与实际负荷相匹配，Histarinol 与对照之间存在显著差异，但在预期阶段则没有差异。在预期呼吸困难期间，导水管周围灰质的 fMRI 信号明显升高。最后，在预期阶段，与 Histarinol 相关的前扣带皮层的前侧区域的去激活程度反映了疼痛类安慰剂效应的类似反应。这些发现强调了与呼吸困难相关的预期效应的神经基础，这对我们理解呼吸症状的感知具有重要意义。
