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Good news for "wusses": Research links pain sensitivity to gene

People vary greatly in their sensitivity to pain: A tetanus shot's pinprick for one person is another's misery. Now researchers at Johns Hopkins and the National Institute on Drug Abuse (NIDA) report that much of human sensitivity to pain -- and the varied response people have to opiate pain medicines -- has a genetic basis. Many of the differences in pain perception by both mouse and human, the scientists say, are likely due to variation in a single key gene.

In a report in this month's Proceedings of the National Academy of Sciences, the scientists explain why a gene coding for the mu opiate receptor, a molecule that bonds with the body's natural opiates, is the likely candidate for pain sensitivity. This same receptor also forms bonds with morphine, additionally making it a good candidate gene for the differences people experience in pain relief from morphine or morphine-like drugs.

The work should eventually result in pain drugs tailored to a person's individual genetic sensitivities -- a hallmark of genome-based therapy. It also could offer the ability to predict a person's risk of addiction to opiate drugs.

The research involves both mouse and human mu receptor genes. "It's rare to find a gene where the animal evidence for its effect is so strong or has such a clear carryover to human studies," says Hopkins/NIDA neuroscientist George R. Uhl, M.D., Ph.D., who led the study.

The researchers were the first to identify sections of the human and rodent mu receptor gene almost a decade ago. In this new work, they've focused on individual differences in the regulatory parts of the receptor gene in humans and mice -- key areas that control how many mu receptors the gene makes.

Looking at eight different strains of mice, the researchers found links between gene differences in the regulatory area and the numbers of mu receptors mouse tissues displayed. More active forms of the gene mean
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Contact: Marjorie Centofanti
mcentofanti@jhmi.edu
410-955-8725
Johns Hopkins Medical Institutions
19-Jul-1999


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