Rein on pain lays mainly in the brain, researchers find

Angela Wyant

Sean Mackey has found that people can use real-time functional magnetic resonance imaging to reduce their pain while viewing images of their brains.

Chronic pain sufferers may be able to reduce pain levels by studying their own live brain images, researchers at the School of Medicine report in a new study.

With training in an investigational technique called "neuroimaging therapy" and the use of high-tech imaging equipment, subjects were able to influence their pain by controlling activity in one of the pain centers of the brain through the use of mental exercises and by visualizing their own brain activity in real time.

Compare it to exercising your muscles in a top-of-the-line weight room. After repeated practice, you get better at it.

The scientists are hopeful that the new technique will be used in the future as a long-term treatment for chronic pain patients—possibly even without all the high-tech equipment. They caution that significantly more work is needed before it can be thought of as a clinical treatment. "We believe these subjects and patients really learned to control their brain and, through that, their pain," said Sean Mackey, MD, PhD, assistant professor of anesthesia and co-author of the study in the Dec. 12 online issue of the Proceedings of the National Academy of Sciences.

The study posed two questions: "Can healthy subjects and patients with chronic pain learn to control activity in specific regions of their brain? And, in doing so, does this lead to an improved control of their pain?" The answer to both was a resounding: "Yes."

"I got incredibly jazzed by the results," said Mackey, who is also associate director of the medical center's pain management division. "However, significantly more science and testing must be done before this can be considered a treatment for chronic pain." A second, larger study is under way to test the potential for long-term use in future therapy.

The researchers used a new technology called real-time functional magnetic resonance imaging, or rtfMRI. The scientists placed subjects inside an MRI scanner where they were able to watch the subjects' brain activity on a moment-by-moment basis. The subjects were then shown "live" action images of their rostral anterior cingulate cortex, an area of the brain responsible for processing pain.

Next, subjects and patients were asked to try various mental strategies to change their brain activity. "As an example, we asked them to think about changing the meaning of the pain," Mackey said. "Instead of thinking of it as a terrible experience, to think of it as something relatively pleasant. Over time, subjects showed an increased ability to change their brain and by doing so to modulate their pain."

How did they do it exactly? "We really don't know, but then we really don't know how anyone controls their brain to perform an action," Mackey said.

Laura Tibbitts, 31, a subject in the study who suffers from back pain caused by a horseback riding accident seven years ago, said she used different thoughts to decrease the pain while watching her "brain on pain."

"I'd think of little people on my back digging out the pain, or I'd think of snowflakes," she said. "The goal was to exercise your brain, to retrain it. Sometimes I felt like I had made a change in my brain. The pain was never completely gone, but it was better."

Mackey said extensive controls were used in the study to make sure the results reflected a direct correlation between brain imaging and pain control.

"One of the questions that always comes up is, 'Did we just design the world's most expensive placebo?'" Mackey said. Researchers used multiple control groups to ensure against this: The first remained outside the MRI machine; the second received no imaging feedback; the third was shown different areas of the brain that don't process pain; and members of the fourth group were shown someone else's brain activity. None of the control subjects showed an ability to control pain levels.

"Real-time functional neuroimaging is a wonderful tool for investigating the neurosystems in the brain responsible for the perception and processing of pain," Mackey said. "It allows us to do that in ways that we've never been able to before."

The study, which included 36 healthy subjects and eight patients with chronic pain, was co-sponsored by researcher Christopher deCharms and his Bay Area company, Omneuron Inc. Mackey and his Stanford collaborators have no financial ties to the company. The study was co-funded by the National Institutes of Health and Stanford University.

Other Stanford researchers involved in the study include Fumiko Maeda, research associate; Gary Glover, professor of radiology, and John Pauly, associate professor of electrical engineering. Former Stanford collaborators include David Ludlow, Deepak Soneji and John Gabrieli.