Analgesic gene
The suffering of thousands of volunteers revealed the truth about the pain gene
Membrane based on ScienceNOW: Pain's in the GenesAlmost the whole life of a person is written in his genome – scientists are becoming more and more convinced of this.
This time, a place and corresponding variations were found in the genetic code that determine the threshold of pain sensitivity of people. The researchers believe that the current discovery will create the perfect painkiller.
Over the past five years, geneticists have linked three serious disorders that lead to an incorrect perception of pain by the body with mutations in the SCN9A gene. In all cases, certain genetic variations influenced the structure of the protein controlling the Na v 1.7 channel, through which sodium enters nerve cells when a pain stimulus appears. (The picture on the left shows the section of the axon in which the SCN9A protein glows red.)
In two out of three cases, people suffered from pain due to the fact that the "wrong" version of the gene caused the sodium channel to either open too easily, or prevented it from closing later. In the third case, the protein encoded by SCN9A did not function at all, as a result, people were not able to feel pain at all.
"We decided to find out whether code variations in this gene can determine the human degree of sensitivity to pain," says Geoffrey Woods from the Cambridge Institute of Medical Research, who discovered a genetic link in the third group of patients mentioned above.
To do this, Woods and his colleagues from different countries investigated differences in the structure of SCN9A in 578 osteoarthritis patients and found 27 single nucleotide polymorphisms (SNPs), that is, permutations of amino acids in DNA. Then biologists compared their presence with the pain threshold of patients, in each case paying attention to the severity of the disease.
One of the SNPs found was present in about 10% of the study participants, and its presence led to a significant increase in pain. (Unfortunately, the threshold of sensitivity is a subjective value, but so far scientists can only focus on the words of a person.)
Four manifestations of the operation/breakdown of the Nav1 channel.7. Various diseases are listed above,
leading to certain violations in the registration of pain sensations
(WT, wild type – "wild type", normal state without mutations).
Next, the geneticists compared the presence of this altered part of the code and pain in 195 patients from Finland suffering from sciatic nerve inflammation, 100 Danes "feeling" phantom pain in amputated limbs (phantom limb pain), 179 people who had an intervertebral disc removed to relieve them of lower back pain, and 200 patients with pancreatitis (inflammation of the pancreas).
It is not yet clear whether there is a link between this gene and the development of chronic pain, which affects about 20% of the adult population of the planet. "The genetic variant now discovered may be partly to blame for the fact that some people have more chronic pain than others," comments Macdonald Christie from the University of Sydney.
It turned out that in the first two groups, people experiencing, in their opinion, the most severe pain, the same polymorphism was most often present. In other groups, this was not statistically confirmed, although the trend was also evident.
Then the scientists tested the hypothesis on healthy people. To do this, they asked 186 women to tell about their pain when exposed to strong heat. And this time it turned out that the lower pain threshold was in those study participants who had a certain variation in SCN9A.
In an article by Wood's group published in the open access in PNAS (Frank Reimann et al., Pain perception is altered by a nucleotide polymorphism in SCN9A), the authors make the following comparison: people who do not have an "incorrect" version of the gene in their genome, nature has, as it were, endowed with a natural painkiller.
To understand how single-nucleotide polymorphism lowers the pain threshold, biologists have introduced an altered gene into kidney cells (they do not have a channel for sodium). As a result, the cells grew their own channels, which closed less efficiently, which means that the pain signal that could be sent by them to the brain was stronger. However, the effect of genetic variation was extremely insignificant, so it is difficult to say with certainty that it is only the SNP of the gene under study.
Schematic representation of SCN9A and the positions of mutations in it (shown by arrows) responsible for various diseases.
Note that in the groups that Woods and his colleagues studied, 15-18% of people had one copy of the genetic variant (indicated in the figure above as R1150W), about 2-3% had two copies, which makes them even more sensitive to pain.
It is too early to talk about the application of the data obtained in practice. However, Jeffrey is confident that the current discovery will undoubtedly help to develop more effective ways to combat unpleasant sensations, as well as reduce the side effects of painkillers. To do this, it will be necessary to create a drug that can act directly on the protein that opens/closing the sodium channel.
Portal "Eternal youth" http://vechnayamolodost.ru11.03.2010