Overcoming Pain

Why people experience chronic pain, and the power they have to de-intensify it

The Brain as Predictor of Chronic Pain and Illness Relief

Trading the physical examination for a functional MRI of the brain.

Arthritis is one of the most disabling chronic human diseases.

One type of arthritis, rheumatoid arthritis (RA), affects up to1% of the world’s population, and is characterized by pain, swelling, and stiffness of joints, leading to a serious decay of life quality. Pain is the initial and prevailing symptom of the disease, leading to immobility, which in turn causes complications such as osteoporosis and cardiovascular disease, and chronic pain. During the last 10 years, the pharmacologic treatment of diseases such as RA has substantially improved because of the development of cytokine blocking agents.

Blocking one of those cytokines, TNF-α, has emerged as a particularly successful therapeutic strategy, and a money-maker for many pharmaceutical concerns. The therapeutic success of neutralization of joint inflammation is based on the breakdown of the inflammatory cytokine network in the affected joint, which results in an improvement of the signs and symptoms of the disease. It has, however, always been stunning how rapidly the blockade of TNF-α improves the patient’s condition, in particular because diseases like RA are highly chronic, building up a vast amount of inflammatory tissue, and leading to irreversible damage of the cartilage and the bone. Thus, rapid resolution of this highly organized inflammatory tissue or tissue damage is very unlikely to explain the fast effect of TNF-α blockade.

So, what is making patients feel better before their joints look better? I recall many patients describing an almost euphoric feeling upon starting one of the TNF-α-blocking drugs. Some research the last few years seems to be telling us that good old-fashioned emotion is leading the leading wave of feeling better: Mice and humans with inflammatory arthritis have been shown to have enhanced brain activity in centers involved in pain perception and the control of emotions. TNF-α-blocking treatment actually reverses this enhanced central nervous system activity in both mice and humans within 24 hours—before clinical effects on arthritis are observed.

In a paper published last year in “Arthritis and Rheumatism,” researchers at NIH and Stanford described what they found when they searched for answers in the brain to the question of why only about 50% of RA patients have major improvements with TNF-blocking agents. Researchers used functional magnetic resonance imaging (MRI) of the brain, MRI of the hand, and clinical assessment of arthritis before and after patients began TNF-inhibiting therapy.

Interestingly, the data showed that RA patients with high-level pain-related brain activity responded better to the therapy than those patients with a low-activation state. Chronic inflammation triggers signals to the brain, as is seen with other chronic pain states. The functional MRI showed enhanced activity in the parts of the brain that deal with chronic pain processing. This fits in with the central sensitization theory of chronic pain; many thought leaders have felt all along that inflammation is a key trigger of the noxious chronic pain loops that stay activated in the chronic pain patient.

For RA—and probably other inflammatory illnesses—the immune system acts as a sort of sensory organ, participating in the transmission of information about tissue damage and joint swelling to the brain. Perhaps the immune system is exquisitely sensitive, perhaps even prescient, when it comes to sensing what drugs are going to work for a given patient.

Someday, it might not be necessary to use trial and error to determine what sort of therapy to use on patients suffering from the chronic pain of autoimmune illness. We rheumatologists won’t be examining swollen joints, but instead looking at the brain imaging on an MRI monitor.

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Mark Borigini, M.D., is a board-certified rheumatologist who has devoted his career to treating illnesses that cause chronic pain and disability.

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