Further, the number of years that patients have pain affects neuronal plasticity, and this plasticity is partially reversible, he says. In one study, in which osteoarthritic patients’ brain anatomy was compared before and after knee joint surgery, the relief of pain correlated with partial recovery of gray matter density.
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All their studies examined only knee pain in osteoarthritis. However, Dr. Apkarian said he does not expect their data to differ for osteoarthritic pain in other joints.
Predicting Placebo Responders
In a new blinded, controlled clinical trial, Dr. Apkarian and his colleagues applied fMRI to predict, with greater than 95% accuracy, which arthritic patients would respond to an inactive placebo medication, he said. They studied the effects on the brain of a placebo in 17 patients with osteoarthritis, who underwent fMRI at baseline and after two weeks of receiving placebo.
Eight patients responded to the placebo (defined as at least a 20% difference in pain), with a greater than 50% pain reduction overall; the other nine patients showed no response. After they stopped taking the placebo, however, the responders had an increase in pain that returned to baseline level and was similar to that of nonresponders.
By comparing brain connectivity using fMRI, Dr. Apkarian and his coinvestigators identified a second brain circuit that differentiated and accurately predicted the placebo responders from the nonresponders. This method could allow researchers to one day “tease out” placebo responders and exclude them from a clinical trial of an experimental medication, he said. Although pain is the main symptom that patients with arthritis complain about, the source and exact type of pain are unclear, session moderator Najia Shakoor, MD, told The Rheumatologist. Dr. Shakoor, who is associate professor of medicine in the rheumatology section at Rush University Medical Center in Chicago, said Dr. Apkarian’s research is “unraveling mechanisms behind pain in arthritis.” She added, “What is fascinating about functional MRI is we can begin to tie what the patient feels physically to what is going on in their brain. It also helps us understand that the placebo effect may be determined by functional differences in the brain [of placebo responders].”
Clinical Applications of Brain Signatures
Dr. Apkarian believes that his research has future clinical applications. “The specificity of the brain signature for each clinical condition is exciting because it gives us the opportunity to develop targeted therapies,” said Dr. Apkarian, whose work has received funding from the National Institutes of Health and Eli Lilly and Company.