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A functional magnetic resonance imaging study on the neural mechanisms of hyperalgesic nocebo effect.

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.

Pubmed ID: 19052227

Authors

  • Kong J
  • Gollub RL
  • Polich G
  • Kirsch I
  • Laviolette P
  • Vangel M
  • Rosen B
  • Kaptchuk TJ

Journal

The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

December 3, 2008

Associated Grants

  • Agency: NCCIH NIH HHS, Id: K01 AT003883
  • Agency: NCCIH NIH HHS, Id: K01 AT003883-01
  • Agency: NCCIH NIH HHS, Id: K01 AT003883-02
  • Agency: NCCIH NIH HHS, Id: K01 AT003883-03
  • Agency: NCCIH NIH HHS, Id: K01-AT003883
  • Agency: NCCIH NIH HHS, Id: K24 AT004095
  • Agency: NCCIH NIH HHS, Id: K24 AT004095-01
  • Agency: NCCIH NIH HHS, Id: K24 AT004095-02
  • Agency: NCCIH NIH HHS, Id: K24-AT004095
  • Agency: NCRR NIH HHS, Id: M01 RR001066
  • Agency: NCRR NIH HHS, Id: M01 RR001066-298648
  • Agency: NCRR NIH HHS, Id: M01 RR001066-305063
  • Agency: NCRR NIH HHS, Id: M01 RR001066-318211
  • Agency: NCRR NIH HHS, Id: M01-RR-01066
  • Agency: NCCIH NIH HHS, Id: P01 AT002048
  • Agency: NCCIH NIH HHS, Id: P01 AT002048-01
  • Agency: NCCIH NIH HHS, Id: P01 AT002048-02
  • Agency: NCCIH NIH HHS, Id: P01 AT002048-03
  • Agency: NCCIH NIH HHS, Id: P01 AT002048-04
  • Agency: NCCIH NIH HHS, Id: P01 AT002048-05
  • Agency: NCCIH NIH HHS, Id: P01 AT002048-050005
  • Agency: NCCIH NIH HHS, Id: P01 AT002048-056371
  • Agency: NCCIH NIH HHS, Id: P01 AT002048-05S1
  • Agency: NCCIH NIH HHS, Id: P01-AT002048
  • Agency: NCRR NIH HHS, Id: P41-RR14075
  • Agency: NCCIH NIH HHS, Id: R21 AT001922
  • Agency: NCCIH NIH HHS, Id: R21 AT001922-01A1
  • Agency: NCCIH NIH HHS, Id: R21 AT001922-02
  • Agency: NCCIH NIH HHS, Id: R21-AT00949

Mesh Terms

  • Adult
  • Brain
  • Brain Mapping
  • Cognition
  • Conditioning (Psychology)
  • 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