Gene variants found in Neanderthals linked to heightened pain sensitivity.

A recent study led by UCL researchers has revealed that individuals harboring three specific gene variants inherited from Neanderthals tend to be more sensitive to certain types of pain. This discovery, published in Communications Biology, adds to the growing body of evidence highlighting how past interbreeding with Neanderthals has left a genetic imprint on modern humans.

The study focused on the SCN9A gene, which plays a role in sensory neurons, and found that those carrying all three Neanderthal variants—M932L, V991L, and D1908G—were more responsive to pain from skin pricking, particularly following exposure to mustard oil. While previous research had identified these variants in Neanderthal genomes and noted increased pain sensitivity in humans possessing them, the specific sensory responses affected remained unclear.

An international team, comprised of researchers from UCL, Aix-Marseille University, University of Toulouse, Open University, Fudan University, and Oxford University, and partially funded by Wellcome, conducted pain threshold measurements on 1,963 individuals from Colombia using various stimuli.

The SCN9A gene encodes a sodium channel highly expressed in sensory neurons responsible for detecting signals from damaged tissue. The study found that the D1908G variant was present in approximately 20% of chromosomes in this population. Of those carrying this variant, about 30% also had the M932L and V991L variants.

The researchers determined that these three variants were linked to a lower pain threshold when subjected to skin pricking after exposure to mustard oil, but not in response to heat or pressure. Moreover, individuals with all three variants exhibited greater pain sensitivity compared to those with only one.

Upon analyzing genetic data from 5,971 individuals across Brazil, Chile, Colombia, Mexico, and Peru, the authors observed that these Neanderthal variants were more prevalent in populations with higher proportions of Native American ancestry, such as the Peruvian population, which boasted an average Native American ancestry of 66%.

The researchers hypothesize that these Neanderthal variants may heighten sensitivity in sensory neurons by altering the threshold for generating a nerve impulse. They speculate that the prevalence of these variants in populations with significant Native American ancestry could be attributed to random chance and population bottlenecks during the initial settlement of the Americas. While acute pain serves to modify behavior and prevent further harm, the scientists emphasize the need for further research to ascertain whether possessing these variants and heightened pain sensitivity might have conferred evolutionary advantages in human development.

Dr. Kaustubh Adhikari, co-corresponding author and researcher at UCL Genetics, Evolution & Environment and The Open University, noted previous research indicating that humans also inherited genetic traits from Neanderthals influencing the shape of our noses.

Dr. Adhikari stated, “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.”

“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.”

Dr. Pierre Faux, first author from Aix-Marseille University and University of Toulouse, added, “We 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 just one of many factors, including environment, past experience, and psychological factors, which influence pain.”

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