ACR 2011: Is There a Unique Brain Signature Associated with Osteoarthritis and Other Chronic Pain Conditions?

Researchers using fMRI claim that the unique structural changes observed in the brains of patients with osteoarthritis can be used to predict placebo response.

During his session Sunday at the 2011 ACR/ARHP Annual Meeting, A. Vania Apkarian, PhD, professor of physiology, department of physiology, Northwestern University Feinberg School of Medicine, summarized recent research on pain perception that shows distinct regional changes in the brains of patients suffering from chronic painful conditions such as osteoarthritis (OA).

Apkarian noted that research has shown that the anatomy of the brain changes profusely in the osteoarthritis pain patient, and said that his research has led him to believe there is a “very specific signature in the brain that distinguishes the OA patient from other chronic pain patients.”

For their research, Apkarian and his team used a mechanical device to apply pressure to the knees of patients, who provided feedback on the extent of pain. They also used functional MRI (fMRI) to identify which parts of the brain are activated, and to what extent, during the painful stimulus. This allows researchers to capture the time variability of the pain and the intensity of the stimulus applied.

He said that psychophysically, pressure pain ratings did not differ between OA patients and healthy subjects. There was also no difference between knees in patients with OA. Thus, he said that “the clinical assumption that the knee joint in OA patient is sensitized to pain turns out not to be true.”

This and other research, said Apkarian, shows that different pain conditions, such as osteoarthritis, produce distinct brain activity, and each has a unique signature in brain. For example, studies show that regional gray matter density shows decreased gray matter in specific regions in patients with chronic back pain (CBP). He said that you can see different patterns of this for different chronic pain conditions, and that chronic pain is associated with functional behavior and chemical changes in the cortex. In addition, Apkarian told the audience that imaging studies show that there is increased interaction between regions of the brain in OA patients compared to healthy subjects. “There is massive plasticity of the brain that is specific to chronic pain patients,” he said.

Because of these changes, he said that researchers can look at the single parameter of whole brain reorganization to distinguish between OA patients and healthy patients with 90% accuracy. The longer the patient has lived with chronic OA pain, the greater the reorganization

Apkarian next described results from a double-blind, placebo-controlled brain imaging study involving 30 patients with chronic back pain: half of them received a 5% lidocaine patch,a nd half received placebo. All patients were scanned with fMRI for spontaneous pain at baseline, at six hours post-treatment, and after two weeks of patch use. The researchers reported no difference in pain perception between treatments. By comparing imaging results of patients who responded to treatment to imaging of nonresponders after 2 weeks, Apkarian said that the research team was able to predict with 80% accuracy at baseline which patients will respond to placebo after two weeks.

In another study, researchers gave placebo to 17 osteoarthritis patients, and conducted fMRI scans at baseline and two weeks post-treatment, then followed the patients two more weeks for pain. After two weeks, there were eight responders to placebo, and nine nonresponders. Responders reported a 50% decrease in pain, vs. no real difference in nonresponders. Pain increased after patients stopped taking placebo.

Investigating whether the same brain network identified in the chronic back pain study was also predictive of placebo response in these patients with OA, Apkarian’s team compared brain connectivity at baseline between the groups and identified a second “brain circuit” that differentiates and predicts OA placebo responders from nonresponders with 95% accuracy.

In closing, Apkarian said that chronic pain imparts a specific signature on the brain, which depends on the experiential history of the condition and reorganizational mechanisms of the peripheral and central nerve systems. He said that there are functional and anatomic profiles that distinguish between acute and various chronic pain conditions, and that it is possible to use the specificity of this signature for each clinical condition to help predict placebo response in patients.

This activity is not sanctioned by, nor a part of, the American College of Rheumatology.