A functional magnetic resonance imaging study on the neural mechanisms of hyperalgesic nocebo effect. J Neurosci 2008 Dec 03;28(49):13354-62
Date
12/05/2008Pubmed ID
19052227Pubmed Central ID
PMC2649754DOI
10.1523/JNEUROSCI.2944-08.2008Scopus ID
2-s2.0-58149396886 (requires institutional sign-in at Scopus site) 221 CitationsAbstract
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.
Author List
Kong J, Gollub RL, Polich G, Kirsch I, Laviolette P, Vangel M, Rosen B, Kaptchuk TJAuthor
Peter LaViolette PhD Professor in the Radiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultBrain
Brain Mapping
Cognition
Female
Functional Laterality
Hippocampus
Humans
Hyperalgesia
Illusions
Magnetic Resonance Imaging
Male
Nerve Net
Neuropsychological Tests
Pain
Pain Measurement
Pain Threshold
Physical Stimulation
Placebo Effect
Young Adult
