Individuals who carry three gene variants inherited from Neanderthals are more sensitive to some varieties of pain, in keeping with a brand new study co-led by UCL researchers.

The findings, published within the journal Communications Biology, are the most recent to point out how past interbreeding with Neanderthals has influenced the genetics of recent humans.

Study: Neanderthal introgression in SCN9A impacts mechanical pain sensitivity. Image Credit: I AM JIFFY / Shutterstock

The researchers found that folks carrying three so-called Neanderthal variants within the gene SCN9A, which is implicated in sensory neurons, are more sensitive to pain from skin pricking after prior exposure to mustard oil.

Previous research has identified three variations within the SCN9A gene, M932L, V991L, and D1908G, in sequenced Neanderthal genomes and reports of greater pain sensitivity amongst humans carrying all three variants. Nonetheless, prior to this study, the precise sensory responses affected by these variants were unclear.

A global team led by researchers at UCL, Aix-Marseille University, University of Toulouse, Open University, Fudan University, and Oxford University, and part-funded by Wellcome, measured the pain thresholds of 1,963 people from Colombia in response to a spread of stimuli.

The SCN9A gene encodes a sodium channel expressed at high levels in sensory neurons that detect signals from damaged tissue. The researchers found that the D1908G variant of the gene was present in around 20% of chromosomes inside this population, and roughly 30% of chromosomes carrying this variant also carried the M932L and V991L variants.

The authors found that the three variants were related to a lower pain threshold in response to skin pricking after prior exposure to mustard oil but not in response to heat or pressure. Moreover, carrying all three variants was related to greater pain sensitivity than having just one.

After 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, akin to the Peruvian population, by which the common proportion of Native American ancestry was 66%.

The authors propose that the Neanderthal variants may sensitize sensory neurons by altering the edge at which a nerve impulse is generated. They speculate that the variants could also be more common in populations with higher proportions of Native American ancestry attributable to random probability and population bottlenecks that occurred in the course of the initial occupation of the Americas. Although acute pain can moderate behavior and forestall further injury, the scientists say additional research is required to find out whether carrying these variants and having greater pain sensitivity could have been advantageous during human evolution.

Previous research by co-corresponding creator Dr Kaustubh Adhikari (UCL Genetics, Evolution & Environment and The Open University) has shown that humans also inherited some genetic material from Neanderthals, affecting the form of our noses.

Dr. Adhikari commented: “Within the last 15 years for the reason that Neanderthal genome was first sequenced, we now have been learning an increasing number of about what we now have inherited from them because of this of interbreeding tens of hundreds of years ago.

“Pain sensitivity is a vital survival trait that permits us to avoid painful things that might cause us serious harm. Our findings suggest that Neanderthals could have been more sensitive to certain varieties of pain, but further research is required for us to grasp why that’s the case, and whether these specific genetic variants were evolutionarily advantageous.”

First creator Dr Pierre Faux (Aix-Marseille University and University of Toulouse) said: “We now have shown how variation in our genetic code can alter how we perceive pain, including genes that modern humans acquired from the Neanderthals. But genes are only considered one of many aspects, including environment, past experience, and psychological aspects, which influence pain.”