Chicago Tribune November 23, 2004

Chronic pain tied to brain changes
Researchers fault treatment delays

By Ronald Kotulak
Tribune science reporter
Published November 23, 2004

Chronic pain appears to damage neurons in key parts of the brain controlling sensory perception, which may explain why such pain becomes harder to treat the longer it lasts, a Northwestern University study has found.

Experts said the research underscores the importance of seeking treatment for chronic pain to avoid long-term damage. Chronic pain may affect as many as 50 million people and is the No. 1 cause of adult disability, according to a survey by the American Chronic Pain Association that also indicates such patients frequently delay seeing a physician.

Loss of brain tissue

Using magnetic resonance brain imaging technology to examine 26 people with chronic back pain, Feinberg School of Medicine physiologist A. Vania Apkarian found their brains had 5 to 11 percent less neocortical gray matter than the brains of normal people--"equivalent to the gray matter volume lost in 10-20 years of normal aging," he wrote in Tuesday's issue of the Journal of Neuroscience.

Brain cells died off in two important areas of the brain that sense and respond to pain signals: the thalamus, which routes sensory information to the cortex in the front of the brain, and the prefrontal cortex, which is involved in interpreting incoming data and making decisions.

"If the elements of the circuitry that one needs to control pain are the ones that we are losing, it may be exactly why we do not have adequate medications for such patients," Apkarian said.

The Northwestern study is the first to show that chronic pain may cause long-term changes in the brain, said Catherine Bushnell of McGill University's Center for Research on Pain in Montreal, who noted that the brain damage increases as the pain continues.

"It's important that pain sufferers seek treatment and that people don't try to be stoic about their pain," she said. "By reducing the pain as quickly as one can, that reduces the probability of having long-term permanent effects."

According to the pain association survey, 72 percent of people with chronic pain have lived with it for more than three years. One out of three has had chronic pain for more than a decade.

A major reason for the high rate of chronic pain, according to experts, is that many people self-treat, are afraid of becoming addicted to painkillers or are inadequately treated by physicians who have not been trained in pain management.

`Major unsolved problem'

In addition, most people with chronic pain continue to suffer despite treatment with anti-epileptic, antidepressant and narcotic drugs, said Dr. Edward Covington, director of the Cleveland Clinic's Chronic Pain Rehabilitation Program.

"All of those work to some extent but all of them are less than fully effective," he said. "This is a major unsolved problem."

Based on the Northwestern findings, Apkarian and his colleagues are developing a new class of drugs designed to protect the areas of the brain damaged by chronic pain. The group has applied for patents on the new compounds and hope to begin human trials.

So far the drugs have produced a significant level of pain control in animal experiments, Apkarian said.

Bushnell, of McGill, who also uses MRIs, has found that people who divert their attention away from pain may calm the brain in ways similar to the effects of potent analgesics.

People mistakenly believe that when they are distracted the pain doesn't bother them as much because they're not thinking about it, she said.

"What we're finding is that when you're distracted from pain there's actually a dampening of the pain information that gets to your cortex," Bushnell said.

"So, it's not just that the pain signals are there and you are learning to ignore them. You're actually engaging systems in the brain that dampen the pain signals," she said.

"It's the same as if you were taking a pain medication to reduce the pain," Bushnell said.

Preventive medication

There is also increasing evidence that treating patients with painkillers before they undergo surgery or other procedures known to be followed by pain can reduce the level of pain later, Covington said.

For example, people who are treated with nerve blocks before amputation often avoid phantom limb pain, he said. Aggressively treating the first outbreak of shingles can reduce the risk of chronic facial pain later, he said.

"We've got lots of evidence coming from different places that if you reduce the impact of pain on the nervous system early, you are likely to mitigate some potentially irreversible changes," Covington said.

Apkarian's group had previously shown that patients suffering from chronic pain experience changes in brain chemistry and that they eventually have problems making decisions that involve emotional subjects.

Effects of chronic pain

The study of 26 chronic back pain patients, who lived with pain for two to 35 years, indicates that the persistent nature of the pain may eventually overwhelm the neuronal circuitry involved in the perception and control of pain.

The frayed circuitry keeps the perception of pain turned on even after treatment with powerful pain-killing drugs, Apkarian explained.

"The faster we treat them the better the outcomes may be," he said. "The longer the atrophy [of brain cells] keeps going, the more elements of the control structures are being lost."

Studies are under way to find out if the brain cells are killed or if they become dormant and can be revived, he said.

Other researchers have found that chronic depression and anxiety can also cause characteristic changes in the brain, but that the pattern of these changes are different than those caused by chronic pain, Apkarian said.