Researchers Pinpoint Brain Region Responsible for Placebo Effect

Finding Could Lead to Personalized Treatment of Chronic Pain

“Research studies have shown that the placebo effect has its own biological properties and has a neurological signature,” said  Marwan Baliki, assistant professor of physical medicine and rehabilitation at Northwestern University Feinberg School of Medicine.“Research studies have shown that the placebo effect has its own biological properties and has a neurological signature,” said Marwan Baliki, assistant professor of physical medicine and rehabilitation at Northwestern University Feinberg School of Medicine.

In the U.S., 100 million people suffer from chronic pain, described as pain that lasts for more than six months.

“Pain is a big burden on the individual and society … it’s a $635 billion burden a year,” said Marwan Baliki, assistant professor of physical medicine and rehabilitation at Northwestern University Feinberg School of Medicine. “The cost and the impact on society is more than diabetes and cancers combined.”

Treating chronic pain with drugs has been a process of trial and error, but new research by scientists at Northwestern Medicine and the Rehabilitation Institute of Chicago could lead to the personalized treatment of chronic pain.

Researchers have discovered a specific region in the brain that’s responsible for the placebo effect in chronic pain sufferers.

Knowing this could allow scientists to “move away from a trial-and-error type of managing pain to a more scientifically based approach,” said Baliki, co-author of the study and research scientist at the Research Institute of Chicago.

“We’re trying to provide the medical community with objective quantifiable markers in the brain that they can use to design specialized management for different types of chronic pain.”

Understanding the Placebo Effect in Chronic Pain

A placebo is a fake treatment that appears to be a real medical treatment. The most well-known example is the use of sugar pills as placebos to measure the effectiveness of drugs in clinical trials.  

Despite being a fake treatment, some people can have a response to placebos. This response—the placebo effect—can be either positive or negative, such as the improvement of a condition or the onset of new symptoms.

Over the past 20 years, research has shown that the placebo effect is “not just some random effect due to no treatment,” Baliki said. “Research studies have shown that the placebo effect has its own biological properties and has a neurological signature.”

Most studies, though, have focused on the placebo effect in healthy patients. This is why Baliki and his colleagues chose to focus on the effect in chronic pain sufferers.

“We tried to pinpoint specific biomarkers on the brain that can predict this,” he said. In order to do this, researchers recruited patients who suffer from chronic knee osteoarthritis pain to participate in a study.

Researchers used resting-state functional magnetic resonance imaging (fMRI) to measure brain activity. (U.S. Navy / Wikimedia Commons)Researchers used resting-state functional magnetic resonance imaging (fMRI) to measure brain activity. (U.S. Navy / Wikimedia Commons)

At the onset of the study, participants reported their levels of pain through various self-reports, including how they would classify their pain on a scale from 0 to 10, with zero being no pain and 10 being the maximum pain.

Researchers used resting-state functional magnetic resonance imaging (fMRI) to “examine brain function in its natural setting without any stimulation or any other manipulation,” Baliki said. This fMRI was performed on all participants at the beginning of the study.

After receiving placebos, participants were surveyed about their levels of pain. About half of the participants reported a decrease in pain, Baliki said. Researchers then compared the fMRI scans of participants who reported a decrease in pain with the images of those who didn’t have a response to the placebo.

Scientists noticed differences in the scans which led them to “identify brain areas initially that can predict the placebo response,” Baliki said. “We found that it predicted a response with around 87 percent accuracy. … We showed that your brain state has the biggest predictor of the placebo response.” 

Given the small study size and focus on chronic knee osteoarthritis pain, Baliki said future studies are needed to validate these findings in different populations and types of chronic pain.

Knowing that someone will respond to a placebo can improve clinical trials for pain drugs because “we can eliminate them from the treatment side,” Baliki said. “This will allow us to look at the efficacy of certain treatments in a more accurate fashion since we can get rid of the placebo effect.”

The findings also pave the way for more customized treatment of chronic pain because the technology can be used to “pinpoint brain areas that predict the efficacy of other drugs, not just placebo response,” he said.

Take opiates, for example. “Some patients respond to opiates. Others don’t,” Baliki said. If researchers can identify which patients will respond to opiates, only those patients would be prescribed them.

“In the future, we hope to be able to provide various biomarkers of the brain that can aid medical staff to ... design personalized types of treatment depending on what we think the efficacy of certain drugs will be to that population of patients,” he said.

Follow Kristen Thometz on Twitter: @kristenthometz


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