(4 of 4)
If the results hold, ultimately, Mackey says, retraining the brain to control the activation of pain pathways may become a powerful way of controlling pain without the dangers of addiction. "The idea is that we can specifically target particular brain regions and processes," he says. "The problem with pain pills is that they go through the entire body and manipulate regions of the brain that we don't want to manipulate."
Retraining the brain has the added advantage of exploiting a part of the pain pathway that so far hasn't been targeted much by drugmakers: its inhibitory arm. While painkilling drugs attempt to dampen already activated pain signals, says Mackey, retraining the brain involves "trying to beef up the muscles that turn down the overall pain experience."
That idea speaks to the brain's plasticity the way it changes and adapts to new situations. A boxer doesn't come into the world unable to feel the pain of a punch in the nose; indeed, he feels it as acutely as anyone else. Over time, however, his pain threshold adjusts so that a punch simply hurts less. Such changes may become self-perpetuating, both for better and for worse.
This kind of resculpting of the brain is leading scientists to explore other ways to rewire the connections that lead to chronic misfiring. David Yeomans, director of pain research at Stanford, was inspired by a psychiatric treatment for bipolar disorder in which magnetic stimulation shuffles nerve networks back to a near normal state. He wondered if the same technique could be applied to pain. And indeed, in early studies, he found that concentrating magnetic fields to target deep-seated pain centers can also relieve symptoms in patients who do not respond to any other therapy.
That's important, since chronic pain may be self-perpetuating, and the sooner pain can be addressed, the less likely it will be to cause persistent and relentless discomfort. "There is intriguing evidence suggesting that chronic pain in osteoarthritis, for example, itself may be causing enhanced damage to joints," says Mackey. "The altered brain is causing changes in the spinal cord that are having an effect on the joints and accelerating damage." The more pain the brain feels, the more damage that does to the body, giving it a physical reason to feel still more.
The Talking Cure
A final, wonderfully low-tech piece of the pain puzzle involves the psychological, social and behavioral factors at play. Whether or not postsurgical pain becomes chronic certainly has a lot to do with a person's genetic sensitivity to activating pain pathways, but it may also depend in part on temperament and mental state. Because brain chemicals that regulate mood and emotion, such as serotonin and norepinephrine, are closely linked to those that govern crisis response including pain it makes intuitive sense that their functions would be intertwined, and doctors see evidence of that all the time.
"Chronic pain really is a disease of the central nervous system," says Borsook. "As such, it is a disease that affects the sensory, emotional, motivational, cognitive and modulatory pathways. And the more we understand in particular the emotional pathways, the more we begin to understand that the traditional way we approach patients in pain may need to be revised."
Borsook is convinced that psychiatrists, who have a good understanding of the brain changes caused by mental illness, can provide insights into how best to exploit them. Patients with depression or anxiety, for example, often report a higher incidence of chronic pain, and their discomfort rises as their depression worsens. In addition, the opioid-based response to pain loops in the same reward and motivational systems that reinforce behaviors like addiction. Treat the depression and you may break the entire pathological cycle.
New research into mental illness, genetics and molecular biology is giving researchers and patients new hope that pain may not have to remain so intractable and untreatable. And rethinking chronic pain as a disease, as a normally adaptive process gone awry instead of as a symptom, may be the key to finding safer and more effective ways of interrupting the hurt.