Chronic pain in osteoarthritis changes the brain and imparts a unique “signature” of morphologic or functional characteristics in the brain that may have future clinical implications, according to research presented at the 2011 ACR/ARHP Annual Scientific Meeting held in Chicago in November.
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A. Vania Apkarian, PhD, a pain researcher and professor of physiology at Northwestern University Feinberg School of Medicine in Chicago, reported his research findings during a presentation entitled “Pain, the Brain, and Osteoarthritis.” [Editor’s note: This session was recorded and is available via ACR SessionSelect at www.rheumatology.org.] He described an interaction between knee pain and the brain in patients with this chronic disease. “The anatomy of the brain in osteoarthritis patients is changing profusely, and it is changing at a rate that we can, in fact, identify,” said Dr. Apkarian. “The brain as a whole network is reorganizing simply by living with pain.”
Using functional magnetic resonance imaging (fMRI) in quantitative psychophysical studies, Dr. Apkarian’s research team studied brain activity in patients with osteoarthritis. The investigational use of this brain-mapping technique captured brain activity while a mechanical pressure stimulus occurred at the position on the knee where patients complained of pain. Patients also underwent fMRI while they subjectively rated their pain using a visual rating task (a finger signal). The investigators conducted the same experiment in healthy participants.
Surprisingly, the researchers found that the knee joint in arthritic patients was not sensitized to the pressure stimulus. The pressure pain ratings, and the brain activity during those ratings, were only minimally different between the patients with arthritis and the healthy people, they observed.
However, fMRI showed less than a 10% overlap in the regions of brain activity for ratings of pressure pain compared with those for ongoing pain such as chronic back pain, said Dr. Apkarian.
Various Pain Types Affect Different Brain Regions
The researchers also studied brain activity while patients rated ongoing osteoarthritis knee pain using well-validated pain scales, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the McGill Pain Questionnaire. Their findings, Dr. Apkarian suggested, indicate that ongoing chronic pain and spontaneous acute pain may have separate brain networks.
Other fMRI studies reported by Dr. Apkarian show different regions of brain activity for osteoarthritis knee pain and for other types of pain, such as allodynia, thermal pain, and fibromyalgia-related pain. In a study of patients with chronic back pain, complex regional pain syndrome, or knee arthritis, he and his coworkers found that gray matter decreased in density in different brain regions depending on the condition. Dr. Apkarian theorized this could mean that, “there is a very specific signature in the brain that differentiates osteoarthritis pain from other pain conditions.”
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.
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.
During the question-and-answer session, a member of the audience disagreed with the speaker’s conclusions about unique, condition-specific brain signatures. “Our group and others in the pain field do not agree that there are specific brain signatures associated with specific pain conditions,” said Daniel J. Clauw, MD, professor of medicine, University of Michigan department of anesthesiology. “You are misinterpreting your data.”
Kathleen Louden is a medical writer based in the Chicago area.