Research team identifies gene mutation that causes loss of pain perception

September 16, 2013 by Bob Yirka, Medical Xpress report
Nurse gives injection to woman, New Orleans, 1941. Credit: Wikipedia.

(Medical Xpress)—A large team of European researchers has identified a gene mutation that is responsible for causing a condition that leads to an inability to experience pain in humans. In their paper published in Nature Genetics, the team describes how they compared the genes of a girl incapable of feeling pain, with the genes of her parents, who do feel pain, and found the gene that was different between them.

People feel pain as a result of excitation of nociceptors— in the skin and other parts of the body that transmit sensory information. The gene the team found is responsible for causing the development of what are known as SCN11A channels. Nociceptors have three such channels, SCN9A, SCN10A and SCN11A. Each works by serving as a passageway for that make their way (carrying pain information) to the spinal cord and eventually the brain. Prior research has found that problems with SCN9A, SCN10A can lead to insensitivity to pain because they cannot transmit the sodium ions. This new research suggests the mutation with SCN11A works in the opposite way—causing too much stimulation to the neuron resulting in a road-block of sorts, preventing the ions from passing through.

The researchers report that they enlisted the assistance of an unidentified girl who was born with an inability to feel pain—a condition that generally leads to multiple injuries as situations that cause injury cannot be felt. Such people they report, tend to burn themselves, experience and engage in activities that result in . By comparing the genes of the girl with her parents, who both experience pain in the normal sense, the team was able to pinpoint the gene that was responsible for the condition in the girl—a mutation that caused SCN11A channels to form incorrectly.

To show that the gene they'd found was the actual culprit, the team caused changes to the same gene in test mice then watched how they behaved. The changed mice began to experience injuries very similar to people who cannot experience pain, supporting their belief they'd found the right gene. In testing with the mice, the researchers found one significant difference—the changes to the gene responsible for creation of SCN11A channels didn't appear to cause complete cessation of sensations—only partial.

Identifying the right genes in humans, the team suggests, may lead to the development of new types of analgesics that can temporarily halt the sensation of pain entirely—a development that would have a profound impact on people who experience pain, regardless of the source.

Explore further: Pain can be contagious

More information: A de novo gain-of-function mutation in SCN11A causes loss of pain perception,

Abstract
The sensation of pain protects the body from serious injury. Using exome sequencing, we identified a specific de novo missense mutation in SCN11A in individuals with the congenital inability to experience pain who suffer from recurrent tissue damage and severe mutilations. Heterozygous knock-in mice carrying the orthologous mutation showed reduced sensitivity to pain and self-inflicted tissue lesions, recapitulating aspects of the human phenotype. SCN11A encodes Nav1.9, a voltage-gated sodium ion channel that is primarily expressed in nociceptors, which function as key relay stations for the electrical transmission of pain signals from the periphery to the central nervous system. Mutant Nav1.9 channels displayed excessive activity at resting voltages, causing sustained depolarization of nociceptors, impaired generation of action potentials and aberrant synaptic transmission. The gain-of-function mechanism that underlies this channelopathy suggests an alternative way to modulate pain perception.

Related Stories

Pain can be contagious

May 8, 2013
(Medical Xpress)—The pain sensations of others can be felt by some people, just by witnessing their agony, according to new research.

Researchers identify which sensory nerve cells contribute to chronic nerve pain

August 17, 2012
(Medical Xpress) -- New research from the University of Bristol has identified the subtypes of sensory nerve cells that are likely to contribute to long-term nerve pain from partial nerve injury. It is hoped this will aid ...

Study reveals target for drug development for chronic jaw pain disorder

August 1, 2013
Temporomandibular joint disorder (TMJD) is the most common form of oral or facial pain, affecting over 10 million Americans. The chronic disorder can cause severe pain often associated with chewing or biting down, and lacks ...

Researchers discover link between expression of GATM and pain associated with statins

August 29, 2013
(Medical Xpress)—A large team with members from several research institutions across the U.S. has found a possible link between the expression of the gene for glycine amidinotransferase (GATM) and pain experienced by patients ...

Recommended for you

The surprising role of gene architecture in cell fate decisions

January 16, 2018
Scientists read the code of life—the genome—as a sequence of letters, but now researchers have also started exploring its three-dimensional organisation. In a paper published in Nature Genetics, an interdisciplinary research ...

How incurable mitochondrial diseases strike previously unaffected families

January 15, 2018
Researchers have shown for the first time how children can inherit a severe - potentially fatal - mitochondrial disease from a healthy mother. The study, led by researchers from the MRC Mitochondrial Biology Unit at the University ...

Genes that aid spinal cord healing in lamprey also present in humans

January 15, 2018
Many of the genes involved in natural repair of the injured spinal cord of the lamprey are also active in the repair of the peripheral nervous system in mammals, according to a study by a collaborative group of scientists ...

The coming of age of gene therapy: A review of the past and path forward

January 11, 2018
After three decades of hopes tempered by setbacks, gene therapy—the process of treating a disease by modifying a person's DNA—is no longer the future of medicine, but is part of the present-day clinical treatment toolkit. ...

Large-scale study to pinpoint genes linked to obesity

January 10, 2018
It's not just diet and physical activity; your genes also determine how easily you lose or gain weight. In a study published in the January issue of Nature Genetics, researchers at the Icahn School of Medicine at Mount Sinai ...

Identical twins can share more than identical genes

January 9, 2018
An international group of researchers has discovered a new phenomenon that occurs in identical twins: independent of their identical genes, they share an additional level of molecular similarity that influences their biological ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

beleg
1 / 5 (1) Sep 16, 2013
Diagnostic checklists include pain.
That guides genetic research - as in this case - too.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.