Thursday, November 15, 2007

The Brain in Chronic Pain

Sophisticated brain-imaging studies suggest new ways to treat chronic pain.

By Emily Singer

Pain relief: Imaging studies have indentified brain areas gone awry in people with chronic pain. Credit: Technology Review

Anyone who suffers from chronic pain knows that the experience is fundamentally different from enduring a scratch or a broken toe. Growing evidence from brain-imaging studies supports this notion: people with chronic pain show fundamental differences in both the structure and function of their brain. Scientists are now using these findings to develop and test new drugs created specifically for chronic pain.

"It should eventually be possible to identify patterns of brain activity involved in perpetuating chronic pain, and then to introduce interventions that we know from published evidence can block or compete with those patterns," says Richard Chapman, director of the Pain Research Center at the University of Utah, in Salt Lake City.

Chronic pain is one of the biggest medical health issues in the Western world; it costs the United States about $150 billion a year. Unlike with acute pain, the causes of chronic pain are often unclear--for example, doctors can identify a physical source in only about 10 percent of those with chronic back pain. A growing number of studies suggest that chronic pain should be viewed as a progressive disease, likely triggered by aberrant but potentially permanent changes in the brain.

The painkillers that help headaches and broken bones do little for chronic pain, leaving a huge need for new treatments. But developing them has been difficult. Perception of pain depends strongly on our level of attention and our emotional state--two factors that are difficult to study in animal models. "We don't have one drug developed from preclinical models of pain that works for chronic pain," says Irene Tracey, a scientist at the University of Oxford, in England, who studies pain.

Now scientists are aiming to develop and test new drugs using human brain imaging. A. Vania Apkarian and his colleagues at Northwestern University have found a series of abnormalities in the brains of chronic pain sufferers: the part of the prefrontal cortex linked to decision making appears to have shrunk in chronic pain patients. And another part of the prefrontal cortex linked to emotion is hyperactive. In fact, a unique study assessing background pain in chronic back-pain patients suggests that the constant pain these people experience is linked to activity almost entirely in emotion-regulating parts of the brain.

Researchers used functional magnetic resonance imaging (fMRI), which measures brain activity, to study background pain. They asked back-pain patients to continually rate their pain while lying in the scanner, and then the researchers compared brain activity patterns during periods of constant pain with those during periods of worsening pain.

While activity patterns during flare-ups resembled those previously linked to acute pain, the pattern associated with constant background pain was distinct: it centered on the medial prefrontal cortex, a brain area involved in emotion and sense of self. "It almost seems like they've turned off the sensory part and are suffering entirely from the emotional aspect," Apkarian says.

Given these findings, the scientists are beginning human tests of a compound called d-cycloserine, an FDA-approved antibiotic that also blocks certain receptors in the brain. (It is currently being tested for treating post-traumatic stress disorder and other conditions.) "We think it increases transmission within the prefrontal cortex to better control the emotional component of pain," says Apkarian. "This will be the first hypothesis-driven test for a pain drug driven by human-imaging studies."