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The Journal of Neuroscience, August 24, 2005, 25(34):7754-7762; doi:10.1523/JNEUROSCI.0439-05.2005
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Behavioral/Systems/Cognitive
Placebo Effects Mediated by Endogenous Opioid Activity on µ-Opioid Receptors
Jon-Kar Zubieta,1,2
Joshua A. Bueller,1
Lisa R. Jackson,1
David J. Scott,1
Yanjun Xu,1
Robert A. Koeppe,2
Thomas E. Nichols,3 and
Christian S. Stohler4
1Department of Psychiatry and Mental Health Research Institute, and Departments of 2Radiology and 3Biostatistics, The University of Michigan, Ann Arbor, Michigan 48109-0720, and 4Office of the Dean, School of Dentistry, University of Maryland, Baltimore, Maryland 21201
Reductions in pain ratings when administered a placebo with expected analgesic properties have been described and hypothesized to be mediated by the pain-suppressive endogenous opioid system. Using molecular imaging techniques, we directly examined the activity of the endogenous opioid system on µ-opioid receptors in humans in sustained pain with and without the administration of a placebo. Significant placebo-induced activation of µ-opioid receptor-mediated neurotransmission was observed in both higher-order and sub-cortical brain regions, which included the pregenual and subgenual rostral anterior cingulate, the dorsolateral prefrontal cortex, the insular cortex, and the nucleus accumbens. Regional activations were paralleled by lower ratings of pain intensity, reductions in its sensory and affective qualities, and in the negative emotional state of the volunteers. These data demonstrate that cognitive factors (e.g., expectation of pain relief) are capable of modulating physical and emotional states through the site-specific activation of µ-opioid receptor signaling in the human brain.
Key words: positron emission tomography; pain; stress; opioid receptors; placebo; human
Received Feb 1, 2005;
revised July 14, 2005;
accepted July 14, 2005.
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