Mutation is behind inability to feel pain

Scientists hope discovery of altered gene may lead to new type of medication, understanding of sensitivity

December 15, 2006|By Michael Stroh | Michael Stroh,Sun reporter

Scientists have pinpointed a simple genetic mutation that bestows seemingly superhuman powers on those born with it: the inability to feel pain.

The discovery, reported yesterday in the journal Nature, came after researchers stumbled onto a 10-year-old boy in Lahore, Pakistan, who entertained crowds by plunging knives through his arm and standing on burning coals without the slightest sign of discomfort.

Researchers eventually traced this ability, which later killed him, to a single altered gene. "It's a remarkable finding," says Birgit Priest, a pain researcher at Merck Research Laboratories in Rahway, N.J. "Given how complex an experience pain is, it's amazing that a single gene could completely abolish it."

The discovery, researchers say, could lead to potent new painkillers and possibly offer clues to why some people are more sensitive to pain than others.

While people who report feeling no pain are extremely rare, scientists have known of their existence for decades. The first well-documented case appeared in 1932, when The Journal of Nervous and Mental Disease described a 53-year-old man who had once performed on the vaudeville stage as "Edward H. Gibson, The Human Pincushion."

During his act, Gibson invited spectators to push sterilized pins into him "anywhere except the abdomen and the groin." Audience members eagerly obliged. By the end of a typical performance, Gibson's body bristled with as many as 60 pins in "up to their heads," the journal noted.

According to the article, Gibson once staged a crucifixion with four razor-sharp gold spikes -- a stunt cut short when a woman in the audience fainted. An assistant had just hammered the first spike through Gibson's hand.

Even after his stage career ended, Gibson told doctors that he would amuse friends by skewering his arms with hypodermic needles and his cheeks with hatpins. Despite this abuse, Gibson's physician wrote in the journal article, "The patient cannot recall any pain except headache -- and his memory is good."

Since the 1930s, scientists have identified several nervous system disorders that result in an abnormal response to painful stimuli.

While the notion of living a pain-free life may sound attractive, it's often anything but, says Dr. Felicia Axelrod, a New York University School of Medicine pediatrician who studies children with these conditions.

People who can't feel pain, she says, are prone to injury and undetected illnesses. Children, for example, inadvertently bite off parts of their tongue or lip and often have their teeth pulled to prevent future accidents.

As they grow older, they can fracture bones or contract dangerous infections without realizing it. "In some ways pain is a gift or a blessing: It does protect you and help you survive," says Axelrod, who knows of 750 people around the world who are incapable of feeling pain.

In the Nature study, C. Geoffrey Woods of the Cambridge Institute for Medical Research in England and colleagues ultimately found six Pakistani children ages 6 to 14 from three related families who had the condition.

What makes these particular children so unusual, scientists say, is that they were otherwise normal. Many of the disorders that render people unable to feel pain also cause mental retardation, excessive sweating and other neurological problems. But the researchers found the Pakistani children had normal cognitive abilities. They could also distinguish between hot and cold drinks, sense the tickle of cotton wool and the pressure of a needle against their skin. They just didn't feel any pain.

"Although the older individuals realized what actions should elicit pain" including acting as if in pain after football tackles, the researchers wrote.

The children did get hurt. Scientists note that several bit off parts of their tongue and suffered fractures. And the young street performer who originally led researchers to their discovery died just before his 14th birthday. He jumped off the roof of a house.

By comparing the children's DNA, scientists found that each carried an inherited mutation in a gene called SCN9A.

SCN9A encodes a protein that serves as a sodium channel. All nerve cells have such channels, which respond to a stimulus by "firing." This is how pain signals get relayed from the body's periphery to the spinal cord and brain.

It's not the first time this particular gene has drawn the attention of pain researchers. In 2004, investigators at Yale University School of Medicine linked SCN9A to another rare abnormality called erythromelalgia. People with this condition experience a painful searing sensation in their feet or hands.

The Yale group discovered that the condition results from a mutant form of SCN9A that causes the nerve's sodium channel to become overactive. In contrast, the Cambridge team found its version of SCN9A caused the sodium channel to be shut off.

Taken together, scientists say these findings suggest the gene could make a promising target for new drugs that alleviate pain from injury or diseases such as cancer.

"We have a target. But there's a lot of work to be done," says Yale neurologist Dr. Stephen Waxman, whose team made the erythromelalgia discovery. "It's one piece of a really fascinating puzzle."

michael.stroh@baltsun.com

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