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Placebo effects mediated by endogenous opioid activity on mu-opioid receptors.

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 mu-opioid receptors in humans in sustained pain with and without the administration of a placebo. Significant placebo-induced activation of mu-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 mu-opioid receptor signaling in the human brain.

Pubmed ID: 16120776


  • Zubieta JK
  • Bueller JA
  • Jackson LR
  • Scott DJ
  • Xu Y
  • Koeppe RA
  • Nichols TE
  • Stohler CS


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

Publication Data

August 24, 2005

Associated Grants

  • Agency: NCCIH NIH HHS, Id: R01 AT 001415
  • Agency: NIDA NIH HHS, Id: R01 DA 016423

Mesh Terms

  • Adult
  • Analgesics, Opioid
  • Brain
  • Humans
  • Male
  • Naloxone
  • Opioid Peptides
  • Pain Measurement
  • Placebo Effect
  • Positron-Emission Tomography
  • Receptors, Opioid, mu