Patients with chronic abdominal pain who received daily placebo pills for three weeks experienced not only improvement in their symptoms, but also showed physiological changes in their brain structures as well, a new UCLA study reveals.
The study, to be published in March in the online edition of the peer-reviewed journal NeuroImage, shows a pathway by which a belief in a placebo produces such changes in pain symptoms.
“We wanted to see how the belief leads to the change in pain symptoms,� said Matthew D. Lieberman, assistant professor of psychology at UCLA and lead author of the study. “This study helps answer that question, and also identifies a neural pathway from a region of the brain associated with placebos and with thinking about emotional experience to a region closely linked to the placebo-related outcome of diminished pain.�
The placebo effect is not just psychological.
“We actually see physical changes in the brain that correspond closely to changes in symptoms that the patients report,� Lieberman said.
Seventy-one percent of the placebo patients afflicted with irritable bowel syndrome (IBS) reported improvement after three weeks. The amount of pain relief reported was very similar for IBS patients who received actual medication to treat the disease, instead of the placebo pills, Lieberman said.
Neuroimaging scans with positron emission tomography (PET) revealed decreased activity in the dorsal anterior cingulate of the patients who reported improvement in their symptoms. Located in the center of the brain, the anterior cingulate has been implicated in pain and the relief of pain.
Why does the anterior cingulate decrease its activity in response to the placebo? The UCLA research team also analyzed the regions of the brain that become more active after patients take the placebos — activity that may inhibit the anterior cingulate response. Among patients who reported improvement in symptoms, the researchers detected a substantial increase in activity in another part of the brain: the right orbitofrontal cortex.
The right orbitofrontal cortex is located behind the forehead and eyes, and has been associated with thinking in words about emotional experiences. This region of the brain also is associated with inhibiting behavior, impulses, emotions and thought.
“In placebo patients whose symptoms were improving, the dorsal anterior cingulate decreased — as if we gave them medication that actually reduced anterior cingulate activity — and the right orbitofrontal cortex increased,� Lieberman said. “These changes in the brain are related; the increase in the right orbitofrontal cortex predicts the extent to which the dorsal anterior cingulate will become less active.
“These changes tell us that the placebo affects the dorsal anterior cingulate associated with the experience of pain, and that this response may be partly a result of placebo-related thoughts about the pain associated with orbitofrontal cortex. Our research suggests that belief about the effectiveness of the placebo is turning on the right orbitofrontal cortex area, which, in turn, may be shutting off the anterior cingulate to some degree.�
The researchers studied 52 patients with IBS, of whom 23 received daily placebos for three weeks. The patients completed a daily diary of symptoms, starting a week before the placebo treatment, and PET neuroimaging tests were performed before and after the three weeks of treatment to monitor changing brain activity of the patients.
Lieberman’s co-authors are Johanna Jarcho, a graduate student in his laboratory; Emeran A. Mayer, director of UCLA’s Center for Neurovisceral Sciences and Women’s Health, and professor of medicine, physiology and psychiatry at the David Geffen School of Medicine at UCLA; Steven Berman, brain imaging head in UCLA’s Neuropsychiatric Institute and Brain Research Institute; Bruce D. Naliboff, a clinical professor in UCLA’s department of psychiatry and biobehavioral sciences; Brandall Y. Suyenobu, a researcher in UCLA’s Brain Imaging Core of the Center for Neurovisceral Sciences and Women’s Health; and Mark Mandelkern, a UC Irvine professor of physics and radiological sciences.
The research was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Mental Health.