Posts tagged pain perception

Researchers may have identified key genes linked to why some people have a higher tolerance for pain than others, according to a study released today that will be presented at the American Academy of Neurology’s 66th Annual Meeting in Philadelphia, April 26 to May 3, 2014.

“Our study is quite significant because it provides an objective way to understand pain and why different individuals have different pain tolerance levels,” said study author Tobore Onojjighofia, MD, MPH, with Proove Biosciences and a member of the American Academy of Neurology. “Identifying whether a person has these four genes could help doctors better understand a patient’s perception of pain.”

Researchers evaluated 2,721 people diagnosed with chronic pain for certain genes. Participants were taking prescription opioid pain medications. The genes involved were COMT, DRD2, DRD1 and OPRK1. The participants also rated their perception of pain on a scale from zero to 10. People who rated their pain as zero were not included in the study. Low pain perception was defined as a score of one, two or three; moderate pain perception was a score of four, five or six; and high pain perception was a score of seven, eight, nine or 10.

Nine percent of the participants had low pain perception, 46 percent had moderate pain perception and 45 percent had high pain perception.

The researchers found that the DRD1 gene variant was 33 percent more prevalent in the low pain group than in the high pain group. Among people with a moderate pain perception, the COMT and OPRK variants were 25 percent and 19 percent more often found than in those with a high pain perception. The DRD2 variant was 25 percent more common among those with a high pain perception compared to people with moderate pain.

“Chronic pain can affect every other part of life,” said Onojjighofia. “Finding genes that may be play a role in pain perception could provide a target for developing new therapies and help physicians better understand their patients’ perceptions of pain.”

(Source: newswise.com)

A girl who does not feel physical pain has helped researchers identify a gene mutation that disrupts pain perception. The discovery may spur the development of new painkillers that will block pain signals in the same way.

People with congenital analgesia cannot feel physical pain and often injure themselves as a result – they might badly scald their skin, for example, through being unaware that they are touching something hot.

By comparing the gene sequence of a girl with the disorder against those of her parents, who do not, Ingo Kurth at Jena University Hospital in Germany and his colleagues identified a mutation in a gene called SCN11A.

This gene controls the development of channels on pain-sensing neurons. Sodium ions travel through these channels, creating electrical nerve impulses that are sent to the brain, which registers pain.

Blocked signals

Overactivity in the mutated version of SCN11A prevents the build-up of the charge that the neurons need to transmit an electrical impulse, numbing the body to pain. “The outcome is blocked transmission of pain signals,” says Kurth.

To confirm their findings, the team inserted a mutated version of SCN11A into mice and tested their ability to perceive pain. They found that 11 per cent of the mice with the modified gene developed injuries similar to those seen in people with congenital analgesia, such as bone fractures and skin wounds. They also tested a control group of mice with the normal SCN11A gene, none of which developed such injuries.

The altered mice also took 2.5 times longer on average than the control group to react to the “tail flick” pain test, which measures how long it takes for mice to flick their tails when exposed to a hot light beam. “What became clear from our experiments is that although there are similarities between mice and men with the mutation, the degree of pain insensitivity is more prominent in humans,” says Kurth.

The team has now begun the search for drugs that block the SCN11A channel. “It would require drugs that selectively block this but not other sodium channels, which is far from simple,” says Kurth.

Completely unexpected

"This is a cracking paper, and great science," says Geoffrey Woods of the University of Cambridge, whose team discovered in 2006 that mutations in another, closely related ion channel gene can cause insensitivity to pain. "It’s completely unexpected and not what people had been looking for," he says.

Woods says that there are three ion channels, called SCN9A, 10A and 11A, on pain-sensing neurons. People experience no pain when either of the first two don’t work, and agonising pain when they’re overactive. “With this new gene, it’s the opposite: when it’s overactive, they feel no pain. So maybe it’s some kind of gatekeeper that stops neurons from firing too often, but cancels pain signals completely when it’s overactive,” he says. “If you could get a drug that made SCN11A overactive, it should be a fantastic analgesic.”

"It’s fascinating that SCN11A appears to work the other way, and that could really advance our knowledge of the role of sodium channels in pain perception, which is a very hot topic,” says Jeffrey Mogil at McGill University in Canada, who was not involved in the new study.

(Source: newscientist.com)