People carrying three Neanderthal variants — known as M932L, V991L, and D1908G — in the gene SCN9A are more sensitive to pain from skin pricking after prior exposure to mustard oil, according to new research.
Analyzing high-density genotype data from 7,594 Latin Americans, Faux et al. characterized Neanderthal introgression in the SCN9A gene. Image credit: Holger Neumann / Neanderthal Museum.
In the study, Dr. Kaustubh Adhikari from University College London and The Open University and his colleagues measured the pain thresholds of 1,963 people from Colombia in response to a range of stimuli.
The SCN9A gene encodes a sodium channel that is expressed at high levels in sensory neurons that detect signals from damaged tissue.
The study authors found that the D1908G variant of the gene was present in around 20% of chromosomes within this population and around 30% of chromosomes carrying this variant also carried the M932L and V991L variants.
They found that the three variants were associated with a lower pain threshold in response to skin pricking after prior exposure to mustard oil, but not in response to heat or pressure.
Additionally, carrying all three variants was associated with greater pain sensitivity than carrying only one.
When they analyzed the genomic region including SCN9A using genetic data from 5,971 people from Brazil, Chile, Colombia, Mexico and Peru, the authors found that the three Neanderthal variants were more common in populations with higher proportions of Native American ancestry, such as the Peruvian population, in which the average proportion of Native American ancestry was 66%.
The researchers propose that the Neanderthal variants may sensitize sensory neurons by altering the threshold at which a nerve impulse is generated.
They speculate that the variants may be more common in populations with higher proportions of Native American ancestry as a result of random chance and population bottlenecks that occurred during the initial occupation of the Americas.
“In the last 15 years, since the Neanderthal genome was first sequenced, we have been learning more and more about what we have inherited from them as a result of interbreeding tens of thousands of years ago,” Dr. Adhikari said.
“Pain sensitivity is an important survival trait that enables us to avoid painful things that could cause us serious harm.”
“Our findings suggest that Neanderthals may have been more sensitive to certain types of pain, but further research is needed for us to understand why that is the case, and whether these specific genetic variants were evolutionarily advantageous.”
“We have shown how variation in our genetic code can alter how we perceive pain, including genes that modern humans acquired from Neanderthals,” said Dr. Pierre Faux, a researcher at Aix-Marseille University and the University of Toulouse.
“But genes are just one of many factors, including environment, past experience, and psychological factors, which influence pain.”
The study was published in the journal Communications Biology.
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P. Faux et al. 2023. Neanderthal introgression in SCN9A impacts mechanical pain sensitivity. Commun Biol 6, 958; doi: 10.1038/s42003-023-05286-z
