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Molecule discovered to be key to pain sensitivity

Sensitivity to pain and the risk of developing chronic pain appear to be influenced by levels of a molecule known to be required for the production of major neurotransmitters. In the November issue of Nature Medicine, an international research team based at Massachusetts General Hospital (MGH) describes this unexpected role for the molecule called BH4 and their findings that a particular set of variations in a human gene involved in synthesizing the molecule appears to reduce pain sensitivity.

"This is the first evidence of a genetic contribution to the risk of developing neuropathic pain in humans. The pain-protective gene sequence, which is carried by about 20 to 25 percent of the population, appears to be a marker both for less pain sensitivity and a reduced risk for chronic pain," says senior author Clifford Woolf, MD, PhD, director of the Neural Plasticity Research Group in the MGH Department of Anesthesia and Critical Care. "Identifying those at greater risk of developing chronic pain in response to medical procedures, trauma or diseases could lead to new preventive strategies and potential treatments."

Previous studies in animals have shown that specific strains or related groups of rodents have significant differences in their risk of developing either neuropathic pain, which results from nerve damage, or inflammatory pain, associated with the immune system's response to injuries or conditions like arthritis. But except for some rare inherited conditions, there has been no evidence that genetics contributed to the risk of neuropathic pain in humans.

The research team had previously used gene chips to find that nerve damage in rats altered the regulation of several hundred genes in associated nerve cells. They began the current study by searching through these genes to find any associated with common metabolic pathways and found that three genes that increased expression in response to nerve damage encoded enzymes involve
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
22-Oct-2006


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