A new study has found out why the African naked mole-rat (Heterocephalus glaber) experiences no pain when exposed to acid. The African naked mole-rat is one of the most unusual mammals in the world. They live in large groups underground in dark narrow burrows where carbon dioxide (CO2) levels are extremely high. CO2 is converted into acid in body tissues, which continuously stimulates pain receptors.
However, investigators of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch have discovered that African naked mole-rats have an altered ion channel in their pain sensors that is inactivated but acid and makes them insensitive to this type of pain. According to Dr. Ewan St. John Smith and Professor Gary Lewin, the animals adaptation to their extreme environment over the course of evolution is the reason for this pain insensitivity.
The Nav1.7 sodium ion channel is vital for transferring painful stimulation to the brain. The channel activates a nerve impulse (action potential) in the pain receptors sensory nerve cells. These cells which are found in the skin feed pain signals to the brain. Sodium ion channel blockers in the form of local anesthetics are already used by Dentists, however these blockers target all sodium ion channels, not just Nav1.7. Individuals with damaged Nav1.7 ion channels as a result of genetic mutation experience no pain, although this is dangerous as infections and minor injuries may go unnoticed, which can often lead to serious consequences.
For the African naked mole-rat this pain insensitivity to acid is clearly a survival advantage, as no other mammals can withstand the high levels of CO2. Usually, high levels of CO2 and acid cause painful burns and activate inflammation in all mammals, including humans. High concentrations of acid can be found in the tissue of individuals suffering with inflammatory joint diseases, such as rheumatism. In the tissue, these high acid levels trigger the pain receptors.
A prior investigation by Professor Lewin found that although African naked mole-rats are insensitive to acid-induced pain they are just as sensitive to heat and pressure as mice. In the American journal Science, Dr. St. John Smith and Professor Lewin reveal that like other mammals, including humans and mice, African naked mole-rats also have the Nav1.7 ion channel. Due to this, the team set out to examine the function of the Nav1.7 ion channel in the African naked mole-rat and in mouse sensory nerves in order to find out if the function of Nav1.7 differs between the two mammals.
In the current investigation, the team found that the ion channel of the African naked mole-rats is different in form and structure that the Nav1.7 ion channel of the mouse or of humans. Ion channels are proteins made up of amino acids, the blueprint of which is coded by the genes. In the naked mole-rat, there are three amino acids in the Nav1.7 ion channel that differ to those in all other mammals. These three changed protein subunits in the naked mole-rat cause extreme impairment or blockage of the Nav1.7 ion channel by acid. Although this phenomenon can be seen in the Nav1.7 ion channel of humans and mice, it is so weak that transmission of pain signals is barely disrupted.
However in the African naked mole-rat this altered ion channel is enough to block signal transmission. According to the team, the cause of this alteration in the Nav1.7 ion channel is due to the mammal’s adaptation over the course of evolution to the high carbon dioxide levels in their habitat, therefore they have become insensitive to this type of pain. This is also why the nerve cells of these mammals other ion channels are activated by acid stimulation that would usually trigger pain sensors.
Researchers have also decoded the structure of the gene for the Nav1.7 ion channel in several other mammals, such as the cave-roosting microbat (Myotis lucifigus), a bat that lives in a similar environment and shows a comparable gene variant. Like the naked mole-rat, the tree-roosting megabat (Pteropus vampyrus) lives in large groups, although it is not exposed to any carbon dioxide pressure. The investigators explain, this indicates that unrelated species living in similar environmental conditions develop similar traits over the course of evolution. This means that for the naked mole-rat, and maybe the cave-roosting microbat, carbon dioxide and acid cannot activate pain.
Significance for individuals with inflammatory diseases?
The pharmaceutical industry is currently working to develop small molecules that will obstruct this ion channel for individuals suffering with inflammatory disease, whose ion channel is continuously activated. Findings from the laboratory of Professor Lewin, might help researchers develop small molecules that specifically block this altered ion channel.
Written by Grace Rattue