Neanderthals may have experienced more pain than average modern humans do, according to new research led by scientists from the Max Planck Institute for Evolutionary Anthropology, Karolinska Institutet and Okinawa Institute of Science and Technology.
Zeberg et al show that a Neanderthal variant of the sodium channel Nav1.7, which is crucial for the initiation of the pain signals, occurs in some humans today. The Neanderthal variant differs from the common variant in its electrophysiological properties and is associated with increased sensitivity to pain. Image credit: Gleiver Prieto.
Neanderthals and their Asian relatives, Denisovans, evolved separately from the ancestors of present-day humans for about 500,000 years. During that time, each group independently accumulated genetic changes that became frequent or fixed.
However, late in their history, Neanderthals and Denisovans mixed with modern humans, which resulted in many genetic variants from these ancient hominins being present in people today.
As several Neanderthal genomes of high quality are now available, it is possible to identify genetic changes that occurred in Neanderthals, investigate their physiological effects, and assess their consequences when they occur in humans today.
One such case is the gene SCN9A, which encodes the Nav1.7 protein, a sodium channel crucial for impulse generation and conduction in peripheral pain pathways.
“Pain is mediated through specialized nerve cells that are activated when potentially harmful things affect various parts of our bodies,” said lead author Dr. Hugo Zeberg, a researcher at the Max Planck Institute for Evolutionary Anthropology and Karolinska Institutet.
“These nerve cells have a special ion channel that has a key role in starting the electrical impulse that signals pain and is sent to the brain.”
Dr. Zeberg and colleagues analyzed 2,535 human genomes from in the 1000 Genomes (1000G) Project and found that some present-day people from Europe and Central and South America carry a Neanderthal variant of the sodium channel Nav1.7.
They also found that carriers of this Neanderthal variant experience more pain.
“The biggest factor for how much pain people report is their age,” Dr. Zeberg said.
“But carrying the Neanderthal variant of the ion channel makes you experience more pain similar to if you were eight years older.”
“The Neanderthal variant of the ion channel carries three amino acid differences — M932L, V991L and D1908G — to the common, modern variant.”
“While single amino acid substitutions do not affect the function of the ion channel, the full Neanderthal variant carrying three amino acid substitutions leads to heightened pain sensitivity in present-day people.”
On a molecular level, the Neanderthal Nav1.7 ion channel is more easily activated which may explain why people who inherited it have a lowered pain threshold.
“Whether Neanderthals experienced more pain is difficult to say because pain is also modulated both in the spinal cord and in the brain,” said senior author Dr. Svante Pääbo, a scientist at the Max Planck Institute for Evolutionary Anthropology and Okinawa Institute of Science and Technology.
“But this work shows that their threshold for initiating pain impulses was lower than in most present-day humans.”
The research is published in the journal Current Biology.
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Hugo Zeberg et al. 2020. A Neanderthal Sodium Channel Increases Pain Sensitivity in Present-Day Humans. Current Biology 30: 1-5; doi: 10.1016/j.cub.2020.06.045
