Brain-imaging studies suggest new ways to treat chronic pain

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Growing evidence from brain-imaging studies supports the idea that patients with chronic pain show fundamental differences in both the structure and function of their brain. Scientists at Northwestern University and Stanford University are now using these findings to develop and test new drugs created specifically for chronic pain, according to Technology Review.

Chronic pain currently costs the United States about $150 billion a year. 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.

A. Vania Apkarian, PhD, and his colleagues at Northwestern University used functional MRI (fMRI), which measures brain activity, to study back pain. They asked back-pain patients to continually rate their back 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.

The results of the study identified 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 while another part of the prefrontal cortex linked to emotion is hyperactive.

According to Apkarian, 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," he said.

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. "We think it increases transmission within the prefrontal cortex to better control the emotional component of pain," said Apkarian. "This will be the first hypothesis-driven test for a pain drug driven by human-imaging studies."

Sean Mackey, MD, a physician and researcher at Stanford University, and his colleagues are studying the brain stem and spinal cord using fMRI. These parts of the nervous system move with every breath and heartbeat, so the researchers had to develop new analysis methods to generate clean images.

Mackey said his studies have shown that chronic pain patients could reduce their pain in the short term using fMRI and researchers are now assessing long-term effects. He said that brain-imaging studies of these patients can shed light on how people learn to control their pain, and which parts of the brain are the most effective targets.

Apkarian and Mackey said that one of the biggest benefits to brain-imaging studies of chronic pain is that they are able to convince both patients and doctors that it really exists. "It's been revolutionary in providing validation to people that pain is something with a real neurological basis," said Mackey. He concluded that physicians can now point to areas of the brain and say, "That's [the] part of the brain that's dysfunctional."