School of Medical Sciences (Neuroscience), Brain and Mind Centre, University of Sydney, Sydney 2006, Australia.
Department of Neuroscience, Monash University, Clayton, VIC 3800, Australia.
Cereb Cortex. 2023 Aug 23;33(17):9822-9834. doi: 10.1093/cercor/bhad247.
Prior experiences, conditioning cues, and expectations of improvement are essential for placebo analgesia expression. The dorsolateral prefrontal cortex is considered a key region for converting these factors into placebo responses. Since dorsolateral prefrontal cortex neuromodulation can attenuate or amplify placebo, we sought to investigate dorsolateral prefrontal cortex biochemistry and function in 38 healthy individuals during placebo analgesia. After conditioning participants to expect pain relief from a placebo "lidocaine" cream, we collected baseline magnetic resonance spectroscopy (1H-MRS) at 7 Tesla over the right dorsolateral prefrontal cortex. Following this, functional magnetic resonance imaging scans were collected during which identical noxious heat stimuli were delivered to the control and placebo-treated forearm sites. There was no significant difference in the concentration of gamma-aminobutyric acid, glutamate, Myo-inositol, or N-acetylaspartate at the level of the right dorsolateral prefrontal cortex between placebo responders and nonresponders. However, we identified a significant inverse relationship between the excitatory neurotransmitter glutamate and pain rating variability during conditioning. Moreover, we found placebo-related activation within the right dorsolateral prefrontal cortex and altered functional magnetic resonance imaging coupling between the dorsolateral prefrontal cortex and the midbrain periaqueductal gray, which also correlated with dorsolateral prefrontal cortex glutamate. These data suggest that the dorsolateral prefrontal cortex formulates stimulus-response relationships during conditioning, which are then translated to altered cortico-brainstem functional relationships and placebo analgesia expression.
先前的经验、条件线索和改善的期望是表达安慰剂镇痛的关键。背外侧前额叶皮层被认为是将这些因素转化为安慰剂反应的关键区域。由于背外侧前额叶皮层的神经调节可以减弱或增强安慰剂效应，我们试图在 38 名健康个体中研究安慰剂镇痛期间背外侧前额叶皮层的生物化学和功能。在使参与者适应期望安慰剂“利多卡因”乳膏缓解疼痛后，我们在 7 特斯拉水平上对右侧背外侧前额叶皮层进行了基线磁共振波谱（1H-MRS）采集。在此之后，我们采集了功能磁共振成像扫描，在这些扫描中，相同的有害热刺激被施加到对照和安慰剂处理的前臂部位。在右侧背外侧前额叶皮层水平，安慰剂反应者和非反应者之间的γ-氨基丁酸、谷氨酸、肌醇或 N-乙酰天冬氨酸的浓度没有显著差异。然而，我们发现谷氨酸这种兴奋性神经递质与条件作用期间的疼痛评分变异性之间存在显著的负相关关系。此外，我们发现右侧背外侧前额叶皮层内存在与安慰剂相关的激活，以及背外侧前额叶皮层和中脑导水管周围灰质之间的功能磁共振成像耦合发生改变，这也与背外侧前额叶皮层中的谷氨酸相关。这些数据表明，背外侧前额叶皮层在条件作用期间形成刺激-反应关系，然后转化为皮质-脑干功能关系的改变和安慰剂镇痛的表达。
