Stabbing back pain or the aches of arthritis send some people to bed in misery while the same distress seems easily tolerated by others. Why does pain hurt some people more than others? Scientists finally have an answer.

It involves a single molecule under control of a gene that acts like a dimmer switch. A “bright” or high setting excites sensory nerves to produce more of a chemical called BH4. For scientists, BH4 has one meaning, but for sufferers, it might as well mean “Big Hurt.” Lower settings block BH4, protecting people from the wrench and bite of chronic pain.

The discovery offers tantalizing hints of “hurt markers” that forecast how people will react to pain. For example, the research results might quickly be adapted for surgery patients. Those with genetic dimmer switches set on “high” would be treated more aggressively with painkillers. Even more intriguing, further investigation may lead to new ways of preventing the onset or continuation of chronic pain.

“This is the first evidence of a genetic connection to the risk of developing chronic pain,” notes Clifford Woolf, Richard J. Kitz Professor of Anaesthesia Research at Harvard Medical School. People who do not have a pain-protective variety of the gene, called GCH1, which controls production of BH4, feel the most pain. Those who inherit one copy from their parents, about 25-30 percent of us, receive enviable protection. Those who are born with two such gene forms, one each from their father and mother, are the luckiest. They comprise about 2-3 percent of the population.

“This gene variant appears to be a marker both for less pain sensitivity and a reduced risk for acute or short-term pain becoming chronic pain,” Woolf points out. “Identifying those at greater risk of developing chronic pain in response to medical procedures, trauma, or diseases could lead to new strategies for prevention and to potential new treatments.”

Woolf is part of an international team, led by researchers from Harvard Medical School and its affiliate Massachusetts General Hospital in Boston, who reported their findings in the November issue of Nature Medicine.

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