Neanderthals were more sensitive to pain.

Nature produces one more clue that if any prehistoric “cave men” were the tough, insensitive brutes, it was our ancestors. Neanderthals, a new gene study has determined, were more sensitive to pain:

Researchers have access to only a few Neanderthal genomes, and most of those have been sequenced at a low resolution. This has made it hard to identify mutations that evolved after their lineage split from that of humans some 500,000–750,000 years ago. But in the past few years, [Svante] Pääbo and his team [at the Max Planck Institute for Evolutionary Anthropology] have generated three high-quality Neanderthal genomes from DNA found in caves in Croatia and Russia. This allows them to confidently identify mutations that were probably common in Neanderthals, yet very rare in humans.

Mutations in a gene called SCN9A — which encodes the NaV1.7 protein — stood out because all of the Neanderthals had three mutations that alter the shape of the protein. The mutated version of the gene was found on both sets of chromosomes in all three Neanderthals, hinting that it was common across their populations.

NaV1.7 acts in the body’s nerves, where it is involved in controlling whether and to what extent painful signals are transmitted to the spinal cord and brain. “People have described it as a volume knob, setting the gain of the pain in nerve fibres,” says [Pääbo’s co-researcher Hugo] Zeberg [of the Karolinska Institute in Stockholm]. Some people with extremely rare genetic mutations that disable the protein do not feel pain, whereas other changes can predispose people to chronic pain.

To investigate how mutations might have altered Neanderthals’ nerves, Zeberg expressed their version of NaV1.7 in frog eggs and human kidney cells — model systems useful for characterizing proteins that control neural impulses. The protein was more active in cells with all three mutations than in cells without the changes. In nerve fibres, this would lower the threshold for conveying a painful signal, says Zeberg.

He and Pääbo then looked for humans with the Neanderthal version of NaV1.7. About 0.4% of participants in the UK Biobank, a genome database of half a million British people, who reported on their pain symptoms had one copy of the mutated gene. No one had two, like Neanderthals. Participants with the mutated version of the gene were about 7% more likely to report pain in their lives than were people without it.

You can read the original research at Current Biology.