The Brain in Chronic Pain

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Another hot target for chronic pain is the modulatory system that humans have evolved to suppress pain when necessary--so that they can run from a predator while wounded, for example. Preliminary evidence suggests that chronic pain sufferers aren't good at recruiting this inhibitory system. Indeed, ongoing studies suggest that people with chronic pain may be hyperactive in the opposite direction: they amplify pain signals on their way to the brain. Sean Mackey, a physician and researcher at Stanford University, and his colleagues are now studying the brain stem and spinal cord, two crucial components of this modulatory system that have traditionally been very difficult to assess with 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.

Identifying the neural signatures linked with chronic pain may also provide a new way to screen experimental drugs for human testing. A small study of pain patients given gabapentin--an epilepsy drug also used to treat nerve pain--showed significant activity changes in the parts of the brain that respond to pain. Drug developers could use this measure as a quick way to assess which experimental compounds to send for further testing, says Tracey, who is developing the technique. "We are getting to the point where we can test novel compounds."

In the absence of effective drugs, many chronic pain patients have turned to behavioral therapies to try to control their pain. Tracey's studies have shown that people who are better at distracting themselves from pain show more activity in a specific part of the pain modulating system. "Maybe we could use brain imaging as a screening tool to determine who would do well on cognitive behavioral therapy," she says.

One of the newest experimental approaches to controlling pain is real-time fMRI, in which patients watch their brain activity in real time as they try to consciously control brain areas involved in pain. (See "Seeing Your Pain.") Mackey and his collaborators have shown that chronic pain patients could reduce their pain in the short term using this method--essentially, a more precisely targeted form of biofeedback--and the researchers are now assessing long-term effects. Mackey says that brain-imaging studies of these patients are shedding light on how people learn to control their pain, and which parts of the brain are the most effective targets.

Scientists don't yet know why some people develop chronic pain and others don't. "There seems to be cortical reorganization at a high level because of the injury itself, but whether that's a coping mechanism or just a consequence, we don't know," says Apkarian. "Some people might be predisposed to chronic pain. But it still seems to get worse as they live with the pain."

He and others say that one of the biggest benefits to brain-imaging studies of chronic pain is that they 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," says Mackey. "We can point to areas of the brain and say, That's part of the brain that's dysfunctional."