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Gaining on pain - Why even the lightest touch can be agony for those with damaged nerves

点击量:   时间:2017-07-05 01:02:13

By Nell Boyce MILLIONS of people who live with untreatable pain could benefit from new insights into how nerves respond to injury, the AAAS heard last week. Some of the latest discoveries could speed up the search for new drugs. People with damaged peripheral nerves, or neuropathy, may endure debilitating pain that fails to respond to conventional painkillers and does not fade with time. It is a common complication of surgery, cancer, diabetes and AIDS. In the worst cases, even a light touch from clothes or a breeze triggers excruciating pain. Life can become so difficult that many patients commit suicide. “Ten years ago we had no idea what caused it and no idea how to treat it,” says Gary Bennett of Allegheny University of the Health Sciences in Philadelphia, who has developed rat models of the condition to test potential treatments. Now, at last, researchers are beginning to unravel some of the mechanisms that underlie the pain. Frank Porreca of the University of Arizona in Tucson has found that changes in the spinal cord may be a key factor. His work focuses on dynorphin, a peptide that accumulates in the spinal cord when peripheral nerves have been damaged. An injection of dynorphin can produce symptoms of neuropathy in rats. The animals struggle to avoid even the slightest touch and seem unusually sensitive to heat. Porreca’s team has located the precise site at which dynorphin binds to receptors for the neurotransmitter NMDA. He believes that drugs that block this site could treat intractable pain: “The identification of a specific binding site offers a new pharmacological target,” he says. Other researchers are looking at other biological changes that accompany neuropathy, including an increase in the number of channels that pump sodium ions across nerve cell membranes, maintaining pain-bearing nerve impulses. Although there are several drugs that can block sodium channels, they work throughout the body, and could have dangerous side effects, damaging heart muscle for instance. However, John Hunter and his colleagues at Roche Bioscience in Palo Alto, California, have discovered a specific kind of sodium channel called PN3 that seems to be largely confined to the peripheral nerves that transmit pain. “These are not widespread in the rest of the nervous system,” says Hunter, whose team will publish its findings next month in The Journal of Neuroscience. He also believes the finding could speed up the search for treatments to ease the misery of neuropathy. “With the development of selective drugs to block PN3, we could develop better treatments than what’s available,