Chronic Pain and the Molding of the Brain

During the past 15 years, research has shown altered structure, function, and chemistry in the brains of patients with chronic pain conditions. Emerging data is helping in the determination as to whether these effects are due to chronic pain—or are factors that drive pain symptoms.

According to research presented at the American College of Rheumatology Annual Scientific Meeting last November, chronic pain in osteoarthritis renders changes in the brain, leaving a unique "signature" of morphologic and functional characteristics that may have an impact on future treatment decisions. In the words of Dr. Apkarian of Northwestern University, "The brain as a whole network is reorganizing simply by living with pain."

Utilizing functional magnetic resonance imaging (fMRI) in quantitative psychophysical studies, his research team studied brain activity in patients with osteoarthritis of the knee, recording brain activity while a mechanical pressure stimulus was applied at the position on the knee where patients complained of pain. Patients also underwent fMRI while they subjectively rated their pain using a finger signal. The same experiments were conducted in a healthy population.

Interestingly, it was found that the knee in the 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 control group. In contrast, fMRI imaging revealed 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. It appears that chronic pain and spontaneous acute pain may have separate brain networks.

Dr. Apkarian presented other fMRI studies, demonstrating different regions of brain activity for knee pain, thermal pain, and fibromyalgia pain. In a study of patients with chronic back pain, complex regional pain syndrome, or knee arthritis, it was shown that brain gray matter became less dense in different brain regions, dependent on the particular condition causing the pain. Furthermore, the relief of pain was correlated with partial recovery of gray matter density.

It is exciting to speculate that perhaps one day fMRI's ability to define brain signatures for specific pain conditions may lead to targeted therapies.

A blinded, controlled study was performed in order to determine which arthritic patients would respond to an inactive placebo medication by performing fMRI on 17 osteoarthritis patients at baseline and two weeks after taking a placebo. Eight patients responded to the placebo; but their pain returned to baseline levels after they stopped taking the placebo. The researchers found another brain circuit that differentiated and accurately predicted those patients who respond to placebo versus those who do not.

The above finding has huge ramifications in the quest to efficiently study new pain treatments, as there is a large placebo effect seen in most pain medication clinical studies: Perhaps researchers will soon be able to apply fMRI as a tool to identify placebo responders and exclude them from a clinical study of an experimental pain therapy.