Ancient human sex changed how some people feel pain

Between 40,000 and 60,000 years ago, humans and Neanderthals got cozy before the latter faded from existence.

We probably didn't feel their pain then, but about 0.4 percent of Britons probably feel it now, thanks to a genetic gift from those the extinct hominids.

A gene variant that can be traced all the way back to Neanderthals, but is still present in about 0.4 percent of modern humans in Britain, may make pain feel even sharper. Out of the 362,944 British citizens in the study, those who had that Neanderthal-derived gene were 7 percent more likely to report at least one pain symptom, compared to those who didn't have the gene.

The authors suggest that translates to feeling the pain typical of someone 8.5 years their senior. Age was correlated with more experiences of pain in the study population.

Hugo Zeberg is the study's first author and a researcher at the Max Planck Institute for Evolutionary Anthropology and The Karolinska Institutet. He tells Inverse that the gene isn't terribly common in Europe –only one percent of Europeans likely have it. Zeberg and his team reached that conclusion by using data collected by the UK Biobank study.

However, follow-ups experiments using data from the 1,000 Genomes Project suggest that 10 percent of East Asians may also have that Neanderthal derived gene, and about 40 percent of "some populations" in Central and South America may have it too, Zeberg says.

Those modern-day humans may be feeling pain in a similar manner to a species that died of tens of thousands of years ago because that gene causes small tweaks to the way the cell sends a pain signal.

The study was published Thursday in Current Biology.

Feeling Neanderthal pain – The gene that Zeberg and his colleagues focused on is called SCN9A. It codes for an ion channel that allows sodium ions (positively charged atoms) to flow in and out of nerve cells in peripheral areas of the body. As the charges inside the cell change, that triggers a signal that tells the brain something is amiss.

The difference between the Neanderthal version of that gene and the modern-day human version is that there are three amino acid substitutions in the Neanderthal gene (amino acids are the building blocks of proteins). These changes all affect the sensitivity of that ion channel, which the team discovered when they engineered ovary cells from aquatic frogs to express those changes.

Those re-engineered cells turned out to have an ion channel that was more likely to activate (open up) in the first place. When that happened, the probability that the gates would stay open also increased in tandem.

"Pain is not necessarily a bad thing."

That tiny cellular change is reflected in how modern-day people with those substitutions feel pain. Those who had all three substitutions were 7 percent more likely to report symptoms of chest pain, knee pain, or leg pain than those with the human version of the gene.

"It is more ready to initiate a pain signal," Zeberg says.

Naturally, it's a little perplexing that a gene that allows people, and Neanderthals, to feel more pain would persist throughout thousands of years. Zeberg says that it's better to think of things the other way around: If we had lost the ability to feel pain, we might actually be in trouble.

There are modern-day cases of people who have one very rare version of that SCN9A gene actually lose the ability to feel pain entirely. The NIH notes that can lead to an accumulation of injuries from wounds to broken bones that "often lead to a reduced life expectancy."

"Pain is not necessarily a bad thing," says Zeberg. And while these pain experiences linked to Neanderthal genes aren't out of the ordinary, they do suggest that Neanderthals had it pretty tough.

What else did Neanderthals leave us? – In May 2010, scientists were able to fully sequence the neanderthal genome. That not only confirmed that ancient humans and Neanderthals got it on, it also showed a number of ways their DNA lives on inside of us.

In 2011, the consumer genetics company 23andMe started offering "Neanderthal ancestry insights." These allow people to see how many of their gene-based traits really come from Neanderthals. Samantha Esselman, the scientist who wrote that report, told Inverse that some human traits are tied to Neanderthal DNA, including being less likely to experience "hanger," less likely to experience a fear of heights, and being more likely to be a hoarder.

That said, connecting genetics and behavior isn't an exact science.

"It is kind of hard to take those very modern terms and modern ideas and try to make that connection back to Neanderthal DNA and how that might influence how you behave," Esselman said.

It's tantalizing to think about what Neanderthals gave us, and what that says about how we behave. Maybe these studies also help us understand why Neanderthals behaved in certain ways too. In the future, we're likely to continue to learn how Neanderthal DNA affects modern-day health.

We already know that they would self-medicate by chewing bark that contains an aspirin-like compound. If these results tell us anything, it's that they had a good reason to, baked right into their DNA.

Abstract: The sodium channel Nav1.7 is crucial for impulse generation and conduction in peripheral pain pathways [1]. In Neanderthals, the Nav1.7 protein carried three amino acid substitutions (M932L, V991L, and D1908G) relative to modern humans. We expressed Nav1.7 proteins carrying all combinations of these substitutions and studied their electrophysiological effects. Whereas the single amino acid substitutions do not affect the function of the ion channel, the full Neanderthal variant carrying all three substitutions, as well as the combination of V991L with D1908G, shows reduced inactivation, suggesting that peripheral nerves were more sensitive to painful stimuli in Neanderthals than in modern humans. We show that, due to gene flow from Neanderthals, the three Neanderthal substitutions are found in 0.4% of present-day Britons, where they are associated with heightened pain sensitivity.