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Assuaging Pointless Pain

For some people with chronic pain--for example, certain cancer patients or people who have suffered nerve injury--even a gentle touch can be excruciating. Now, for the first time, scientists have isolated individual cells in the spinal cord of mice that overreact to heat and touch. By knocking out these cells, they may be able to suppress exaggerated pain sensations, while leaving intact the body's ability to sense normal pain.

The work, by neuroscientist Patrick Mantyh and electrophysiologist Donald Simone of the University of Minnesota, Minneapolis, appears in tomorrow's issue of Science*. The research involved selectively killing mouse nerve cells with a receptor for a neurotransmitter called substance P, one of a cocktail of chemicals released by nerve cells after the nerve ending senses a painful stimulus. Substance P is absorbed by "second-order" neurons in the spinal cord, which transmit the signal up to the brain.

The researchers then injected these mice with capsaicin, the active ingredient in hot peppers. Ordinarily this chemical causes mice--and humans--to become hypersensitive to heat or touch for a few minutes. But the mice with no substance P receptors behaved as if nothing had happened, responding to heat or pokes no more rapidly after receiving capsaicin than beforehand. "I didn't think we'd be able to dissociate the hypersensitive pain response from the normal," says Mantyh, "but that's exactly what happened. This signals a revolution in pain research, in that it suggests you can differentiate these two kinds of pain."

"This work is very important for two reasons," says Steve Hunt, a molecular neuroscientist at the Medical Research Council in Cambridge, England. "They've identified a pathway going up to the brain that seems to control the development of pain states, and they've come up with a method for manipulating that pathway. That's very exciting."

In the future, says Hunt, pharmaceutical companies might be able to attach a drug to substance P that would disable or heal the targeted neurons instead of killing them. Annika Malmsted of the University of California of San Francisco says that such "selective inhibitors"--unlike present drugs such as morphine, which wipe out all pain sensation--might allow chronic pain patients to get back to a more normal life.

*For more information, Science Online subscribers can link to the full text of the Report.