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The experience of pain arises from both physiological and psychological factors, including one's beliefs and expectations. Thus, placebo treatments that have no intrinsic pharmacological effects may produce analgesia by altering expectations. However, controversy exists regarding whether placebos alter sensory pain transmission, pain affect, or simply produce compliance with the suggestions of investigators. In two functional magnetic resonance imaging (fMRI) experiments, we found that placebo analgesia was related to decreased brain activity in pain-sensitive brain regions, including the thalamus, insula, and anterior cingulate cortex, and was associated with increased activity during anticipation of pain in the prefrontal cortex, providing evidence that placebos alter the experience of pain.
The idea that sensory experience is shaped by one's attitudes and beliefs has gained currency among psychologists, physicians, and the general public. Perhaps nowhere is this more apparent than in our ability to modulate pain perception. A special case of this phenomenon is placebo analgesia, in which the mere belief that one is receiving an effective analgesic treatment can reduce pain (1-5). Recently, some researchers have attributed placebo effects to response bias and/or to publication biases (6), which raises the issue of whether placebo treatments actually influence the sensory, affective, and cognitive processes that mediate the experience of pain.
One important piece of evidence that placebo effects are not simply due to response or publication bias is that such effects can be reversed by the mu-opioid antagonist naloxone (2, 3, 7), suggesting that some kinds of placebo effects may be mediated by the opioid system. However, naloxone has also been shown to produce hyperalgesia independent of placebo, in some cases offsetting rather than blocking the effects of placebo analgesia (8). Although pharmacological blockade provides suggestive evidence regarding the neurochemical mechanisms mediating placebo effects, such data do not illuminate the nature of the information-processing system that gives rise to such effects. Neuroimaging data can provide complementary evidence of how pain processing in the brain is affected by placebos and about the time course of pain processing. Identifying placebo-induced changes in brain activity in regions associated with sensory, affective, and cognitive pain processing (9) may provide insight into which components of pain processing are affected by placebo. In addition, identifying changes that occur at particular times-in anticipation of pain, early...