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Pain

Pain

Pain serves as a critical warning signal that alerts the body to potential or actual harm. When mechanical pressure on the skin is intense, such as from a sharp pinch, the sensation transitions from touch to pain. Similarly, extreme temperatures, like a hot pot handle, convert the sensation of heat into pain. Pain can also result from overstimulation of other senses, such as blinding light, loud noise, or the intense heat from habañero peppers. This ability to sense pain is essential for...

Nociception

Nociception

Nociception—the ability to feel pain—is essential for an organism’s survival and overall well-being. Noxious stimuli such as piercing pain from a sharp object, heat from an open flame, or contact with corrosive chemicals are first detected by sensory receptors, called nociceptors, located on nerve endings. Nociceptors express ion channels that convert noxious stimuli into electrical signals. When these signals reach the brain via sensory neurons, they are perceived as pain.

Mechanically-gated Ion Channels

Mechanically-gated Ion Channels

Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...

Voltage-gated Ion Channels

Voltage-gated Ion Channels

Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several...

Non-gated Ion Channels

Non-gated Ion Channels

Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism....

Thermosensation

Thermosensation

Peripheral thermosensation is the perception of external temperature. A change in temperature (on the surface of the skin and other tissues) is detected by a family of temperature-sensitive ion channels called Transient Receptor Potential, or TRP, receptors. These receptors are located on free nerve endings. Those detecting cold temperatures are closer to the surface of the skin than the nerve endings detecting warmth. These thermoTRP channels, while temperature selective, have relatively...

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Related Experiment Video

Updated: Dec 13, 2025

Advanced Glycation End-Products Sensitize Human Sensory-Like Neuron Cells to Capsaicin-Induced Calcium Influx

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A Neanderthal Sodium Channel Increases Pain Sensitivity in Present-Day Humans.

Hugo Zeberg¹, Michael Dannemann², Kristoffer Sahlholm³

¹Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany; Department of Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden.

Current Biology : CB

|July 25, 2020

Summary

Neanderthal variants of the Nav1.7 sodium channel show reduced inactivation, leading to increased pain sensitivity. These genetic traits persist in modern Britons due to ancient gene flow.

Keywords:

Neanderthals gene flow introgression pain sodium channel

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Published on: May 2, 2025

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Published on: February 10, 2023

Area of Science:

Neuroscience
Genetics
Paleontology

Background:

The Nav1.7 sodium channel is essential for pain signal transmission in peripheral nerves.
Neanderthals possessed three specific amino acid substitutions in their Nav1.7 protein compared to modern humans.

Purpose of the Study:

To investigate the functional consequences of Neanderthal Nav1.7 sodium channel variants.
To determine if these variants influence pain sensitivity in modern human populations.

Main Methods:

Electrophysiological analysis of Nav1.7 proteins with various combinations of Neanderthal substitutions.
Genotyping of present-day Britons to identify Neanderthal Nav1.7 variants.

Main Results:

Single amino acid substitutions had no significant effect on Nav1.7 function.
The full Neanderthal Nav1.7 variant and the V991L/D1908G combination exhibited reduced channel inactivation.
These Neanderthal variants are present in approximately 0.4% of modern Britons and correlate with heightened pain sensitivity.

Conclusions:

Neanderthal Nav1.7 variants can lead to increased peripheral nerve excitability and pain sensitivity.
Ancient gene flow introduced these pain-associated variants into the modern human gene pool.
These findings link Neanderthal genetics to observable pain perception differences in contemporary populations.