Fri 20-Feb, 2004
In a series of experiments designed to show how the human brain responds to the “placebo effect,” medical researchers using a novel magnetic resonance imaging study have observed brain activity associated with the pain-reducing effects of a placebo treatment, according to a paper published today in the journal Science.
Placebos are medically inert substances commonly administered to control groups in clinical trials of pharmaceuticals. Results in those control groups are compared with results in the experimental group getting pharmacologically active drugs in order to assess the medical effectiveness of the tested drugs.
The interdisciplinary group of investigators—including scientists from the University of Texas Medical Branch at Galveston (UTMB), Princeton, Harvard, the University of Michigan and the University of Wisconsin—exposed volunteer subjects to pain from electrical shock and heat in two separate studies. In the first, 24 subjects were given electrical shocks on their right wrists after the skin there had been treated with a cream that they had been told would decrease pain. The cream actually had no analgesic properties, but many subjects reported less pain than when shocks were administered after treatment with an identical cream that they were told was inert. Functional magnetic resonance imaging (fMRI) scans correlated with the subjects’ reports: when they were told that the cream applied to their wrists would reduce pain, shocks produced lower activity in pain-sensitive areas of their brains (as measured by blood flow) than did identical shocks when they were told the same cream was an inert “control” substance.
Scientists saw similar results in the second study, in which heat was used instead of electricity and identical creams were applied in two different locations on the left forearm. Almost three quarters of the 50 subjects said they felt less pain on the area of skin coated with the cream they were told relieved pain, and fMRI of the brains of those who reported this placebo effect showed lower pain-center activity consistent with those reports.
Scans conducted during both studies also showed that the placebo effect was tied to increased activity in the prefrontal cortex of the brain, an area associated with anticipation and planning. That led the researchers to conclude that expecting pain relief activates brain mechanisms responsible for the placebo effect.
“Not only is placebo-induced anticipation linked to behavior, but it also links to the actual experience of pain in the part of the brain responsible for recognizing and transmitting pain, the thalamus and associated areas,” said one of the study’s authors, Robert M. Rose, a professor of psychiatry at UTMB and executive director of the John D. and Catherine T. MacArthur Foundation Mind Brain Body and Health Initiative. “The subjects report they have less pain, and while that’s only subjective, they also have the objective changes in the brain mediating pain sensation.”
Those results, Rose said, could have implications that go beyond pain to a whole range of bodily systems influenced by the brain, and beyond the “placebo pill” to include everything a caregiver does to create and maintain a patient’s belief that he or she will get better. “This larger concept of the placebo moves past the inert pharmacological pill to the psychology and changes in the patient’s expectancy, belief and hope that are engendered by the doctor,” Rose said. “We think there’s a real science behind doctors engendering belief and expectancy in patients. The brain is a big regulator of the autonomic nervous system, the hormones and the immune system, which have a major physiological impact.”
The study was funded by the MacArthur Foundation’s Mind Brain Body and
Health Initiative, the Rockefeller Family and Associates, the Kohlberg
Foundation and the National Science Foundation. Functional magnetic resonance
imaging data was collected at Princeton University and the University of
Michigan. In addition to Rose, the other authors of the article were Tor
D. Wager, Edward E. Smith, Alex Sokolik and Kenneth L. Casey of the University
of Michigan, James K. Rilling and Jonathan D. Cohen of Princeton University,
Richard J. Davidson of the University of Wisconsin, and Stephen M. Kosslyn
of Harvard University.
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