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The Journal of Neuroscience, January 11, 2006, 26(2):381-388; doi:10.1523/JNEUROSCI.3556-05.2006

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Behavioral/Systems/Cognitive
Brain Activity Associated with Expectancy-Enhanced Placebo Analgesia as Measured by Functional Magnetic Resonance Imaging

Jian Kong,¹ Randy L. Gollub,^1,2,3 Ilana S. Rosman,¹ J. Megan Webb,¹ Mark G. Vangel,^2,3 Irving Kirsch,⁴ and Ted J. Kaptchuk⁵

¹Department of Psychiatry, Massachusetts General Hospital (MGH), ²MGH/Massachusetts Institute of Technology/Harvard Medical School (HMS) Athinoula A. Martinos Center for Biomedical Imaging, and ³MGH General Clinical Research Center Biomedical Imaging Core, Charlestown, Massachusetts 02129, ⁴School of Applied Psychosocial Studies, University of Plymouth, Plymouth, Devon, PL4 8AA, United Kingdom, and ⁵Osher Institute, HMS, Boston, Massachusetts 02215

In this study, a well established expectancy manipulation model was combined with a novel placebo intervention, a validated sham acupuncture needle, to investigate the brain network involved in placebo analgesia. Sixteen subjects completed the experiment. We found that after placebo acupuncture treatment, subjective pain rating reduction (pre minus post) on the placebo-treated side was significantly greater than on the control side. When we calculated the contrast that subtracts the functional magnetic resonance imaging (fMRI) signal difference between post-treatment and pretreatment during pain application on placebo side from the same difference on control side [e.g., placebo (post – pre) – control (post – pre)], significant differences were observed in the bilateral rostral anterior cingulate cortex (rACC), lateral prefrontal cortex, right anterior insula, supramarginal gyrus, and left inferior parietal lobule. The simple regression (correlation) analysis between each subject's fMRI signal difference of post-treatment and pretreatment difference on placebo and control side and the corresponding subjective pain rating difference showed that significant negative correlation was observed in the bilateral lateral/orbital prefrontal cortex, rACC, cerebellum, right fusiform, parahippocampus, and pons. These results are different from a previous study that found decreased activity in pain-sensitive regions such as the thalamus, insula, and ACC when comparing the response to noxious stimuli applied to control and placebo cream-treated areas of the skin. Our results suggest that placebo analgesia may be configured through multiple brain pathways and mechanisms.

Key words: placebo; placebo analgesia; expectancy; expectancy manipulation; pain; placebo acupuncture needle; Steitberger needle

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Received Aug 22, 2005; revised November 10, 2005; accepted November 11, 2005.

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