Advances Against Chronic Pain

New research offers hope for chronic pain sufferers.

Man massaging elbow in pain
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Rewiring the brain. Researchers at Stanford and the Medical University of South Carolina, among others, are investigating another way to reduce pain, called transcranial magnetic stimulation, which is currently used to treat people with major depression. In this procedure, an 8-inch coil is placed on the head and an electrical current is run through it, creating a magnetic field that causes electrical changes in the brain. According to Kevin Johnson, a research associate at the Stanford pain lab, early experiments suggest that by using a high frequency electrical current to stimulate the primary motor cortex (involved in planning and executing bodily movement), the pain pathways can be disrupted.

Researchers are still puzzling over why this occurs, but it may hinge on the fact that the actions of the motor cortex are closely linked to parts of the central nervous system that control sensory perception, says Johnson. When you move your arm, for example, you can sense its motion even though your eyes may be closed. Pain also has a sensory component. "My best guess is that by stimulating the motor cortex, you're [somehow] overriding sensory perception," including the ability to sense pain, Johnson says. Mackey believes that repeated use of this kind of electrical stimulation can teach the central nervous system to develop alternative sensory pathways that ultimately reduce a patient's sensation of chronic pain.

Researchers at the University of Colorado–Boulder are leading another promising area of study, involving the body's glial cells. In the past, scientists believed that glia existed primarily to support nerve cells. Derived from the Greek word for "glue," glia wrap around the neurons, holding them in place, and perform housekeeping functions such as removing debris, dead neurons, and the like.

But in the past 20 years, researchers have discovered an entirely different role for glial cells in revving up a person's protective pain response. When you have the flu, for example, that muscle soreness you feel is your body's way of encouraging you to remain still and quiet until you heal. When the immune system is activated, glial cells release neuroactive substances that increase the excitability of the spinal cord neurons responsible for relaying pain messages to the brain. They also increase the release of pain-related neurotransmitters from sensory nerve endings. Once activated, glial cells produce proteins called proinflammatory cytokines that exaggerate, or amplify, the body's pain response like the volume knob on a radio, says Linda Watkins, a professor in the department of psychology and neuroscience at UC–Boulder. Under certain conditions, if someone has nerve damage, perhaps, or a virus like HIV that homes in on the central nervous system, glia can become activated and cause a strong pain response that doesn't serve a protective purpose. It's just pain. Researchers are working to develop drugs that block the glia's harmful effects while leaving their housekeeping functions intact.

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"All the current pain drugs target neurons," Watkins explains. "We started looking at how you could target these glial cells very specifically." The team has a grant from NIH to move toward human trials in the next few years of XT-101, a drug that Watkins describes as "Valium for glia," halting the release of proinflammatory cytokines and calming them down to their normal state. In animal trials, the drug blocked neuropathic pain from nerve injury for three months in rats. "The rats say this will work," Watkins says, adding that early trials with dogs also look promising.

At Stanford, researchers looking at glial cells have reported some success in a small study using a drug called naltrexone to inhibit the activity of the cells. (Currently, the drug is approved to treat addiction by blocking the effect of opioids and alcohol on the body.) When researchers gave 10 women with fibromyalgia a very low dose of the drug, their pain symptoms improved more than 30 percent compared with a placebo. "The early information looks very promising," says Mackey. The next step is to move toward larger clinical trials, he says.