Neanderthals May Have Been More Sensitive to Pain Than Most Humans

Modern humans with this Neanderthal-inherited gene report 7 percent more pain than other people

New research suggests a genetic mutation some humans inherited from Neanderthals may make them more sensitive to pain than their peers. Science Photo Library / Daynes, Elisabeth

A new study of Neanderthal DNA suggests our species’ extinct relatives may have been particularly sensitive to pain, reports Ewen Callaway for Nature.

Neanderthals disappeared some 40,000 years ago, but some humans living today retain bits of Neanderthal DNA—evidence that our species once interbred. Though they hunted large, dangerous animalsincluding bison, mammoths and cave bears—in frigid climes, Neanderthals may be the source of a genetic variant associated with increased sensitivity to pain in modern humans, accoring to the new research published last week in the journal Current Biology.

Researchers looking to compare Neanderthals’ DNA to modern humans have historically only had a few low resolution genomes to choose from. But the team behind the new paper were able to produce three high-quality Neanderthal genomes from genetic material recovered from caves in Croatia and Russia, per Nature.

Researchers found a mutation to a gene called SCN9A that encodes a protein involved in sending pain signals to the spinal cord and brain on both chromosomes of all the Neanderthal genomes. Its presence on both chromosomes of all three genomes suggests it was common in the Neanderthal population, according to Nature.

The mutation to SCN9A codes for three amino acid differences compared to modern humans, researchers tell Brooks Hays of United Press International (UPI).

"[The gene] is unusual in having three differences unique to Neandertals in the protein it encodes," Svante Pääbo, a geneticist at the Max Planck Institute for Evolutionary Anthropology and co-author of the study, tells UPI.

Through experiments, the researchers determined that the Neanderthal mutation lowers the threshold required for the body’s nerves to send pain signals to the spinal cord and brain, which could also potentially make those sensations more painful, reports Emma Betuel for Inverse.

“People have described it as a volume knob, setting the gain of the pain in nerve fibres,” Hugo Zeberg, the paper’s lead author and a researcher at the Max Planck Institute for Evolutionary Anthropology as well as the Karolinska Institutet, tells Nature.

The researchers used a database of more than 362,944 genomes of British people to investigate whether this mutation was present in modern humans. Only 0.4 percent of Brits who responded to a questionnaire about their pain symptoms had a copy of the Neanderthal mutation to the SCN9A gene, per Inverse, but those who had the mutation were 7 percent more likely to report pain at least one pain symptom. Though its true older folks in the survey tended to report increased pain, the researchers found that people with the Neanderthal variant to SCN9A were reporting pain typical of someone about 8.5 years older than their actual age.

In an emailed statement to Amy Woddyatt of CNN, Zeberg notes that other genetic variants impact people’s experience of pain that are unrelated to Neanderthal ancestry, and that not everyone with a low pain threshold could blame it on Neanderthals.

"Whether Neandertals experienced more pain is difficult to say because pain is also modulated both in the spinal cord and in the brain," Pääbo says in a statement. "But this work shows that their threshold for initiating pain impulses was lower than in most present-day humans."

Neuroscientist Cedric Boeckx of the Catalan Institute for Research and Advanced Studies tells Nature that, “this is beautiful work.” Boeckx, who was not involved in the research, says the paper shows how studying modern humans can illuminate facets of Neanderthal physiology.

But Gary Lewin, a neuroscientist at the Max Delbrück Center for Molecular Medicine in Germany who was not involved in the research, tells Nature that the effect caused by the Neanderthal mutations to SCN9A is small, especially compared to other mutations associated with chronic pain. Lewin further wonders what adaptive advantage increased pain sensitivity might have conferred.

"Pain is not necessarily a bad thing," Zeberg tells Inverse, noting that bad sensations help us avoid injury and survive.

Zeberg tells CNN that he hopes in the future the findings of genetic investigations such as this one could help develop personalized medical treatments based on the patient’s genes.

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