Kong Jian, Gollub Randy L, Polich Ginger, Kirsch Irving, Laviolette Peter, Vangel Mark, Rosen Bruce, Kaptchuk Ted J
Department of Psychiatry, Massachusetts General Hospital, Massachusetts General Hospital, Massachusetts Institute of Technology/Harvard Medical School Athinoula A Martinos Center for Biomedical Imaging, Boston, Massachusetts 02215, USA.
J Neurosci. 2008 Dec 3;28(49):13354-62. doi: 10.1523/JNEUROSCI.2944-08.2008.
Previous studies suggest that nocebo effects, sometimes termed "negative placebo effects," can contribute appreciably to a variety of medical symptoms and adverse events in clinical trials and medical care. In this study, using a within-subject design, we combined functional magnetic resonance imaging (fMRI) and an expectation/conditioning manipulation model to investigate the neural substrates of nocebo hyperalgesia using heat pain on the right forearm. Thirteen subjects completed the study. Results showed that, after administering inert treatment, subjective pain intensity ratings increased significantly more on nocebo regions compared with the control regions in which no expectancy/conditioning manipulation was performed. fMRI analysis of hyperalgesic nocebo responses to identical calibrated noxious stimuli showed signal increases in brain regions including bilateral dorsal anterior cingulate cortex (ACC), insula, superior temporal gyrus; left frontal and parietal operculum, medial frontal gyrus, orbital prefrontal cortex, superior parietal lobule, and hippocampus; right claustrum/putamen, lateral prefrontal gyrus, and middle temporal gyrus. Functional connectivity analysis of spontaneous resting-state fMRI data from the same cohort of subjects showed a correlation between two seed regions (left frontal operculum and hippocampus) and pain network including bilateral insula, operculum, ACC, and left S1/M1. In conclusion, we found evidence that nocebo hyperalgesia may be predominantly produced through an affective-cognitive pain pathway (medial pain system), and the left hippocampus may play an important role in this process.
先前的研究表明，反安慰剂效应（有时被称为“负面安慰剂效应”）在临床试验和医疗过程中，会对各种医学症状和不良事件产生显著影响。在本研究中，我们采用受试者内设计，结合功能磁共振成像（fMRI）和预期/条件操纵模型，利用右前臂的热痛来研究反安慰剂痛觉过敏的神经基础。13名受试者完成了该研究。结果显示，给予惰性治疗后，与未进行预期/条件操纵的对照区域相比，反安慰剂区域的主观疼痛强度评分显著增加。对相同校准的有害刺激的痛觉过敏反安慰剂反应进行fMRI分析，结果显示包括双侧背侧前扣带回皮质（ACC）、脑岛、颞上回；左侧额盖和顶盖、内侧额回、眶额皮质、顶上小叶和海马体；右侧屏状核/壳核、外侧额回和颞中回在内的脑区信号增强。对同一组受试者的静息态fMRI自发数据进行功能连接分析，结果显示两个种子区域（左侧额盖和海马体）与包括双侧脑岛、脑盖、ACC和左侧初级感觉运动皮层（S1/M1）在内的疼痛网络之间存在相关性。总之，我们发现有证据表明，反安慰剂痛觉过敏可能主要通过情感-认知疼痛通路（内侧疼痛系统）产生，并且左侧海马体可能在此过程中发挥重要作用。
