Navigation Links
MDC researchers: Ion channel makes African naked mole-rat insensitive to acid-induced pain

British researchers of the Max Delbrck Center for Molecular Medicine (MDC) Berlin-Buch have found out why the African naked mole-rat (Heterocephalus glaber), one of the world's most unusual mammals, feels no pain when exposed to acid. African naked mole-rats live densely packed in narrow dark burrows where ambient carbon dioxide (CO2) levels are very high. In body tissues, CO2 is converted into acid, which continuously activates pain sensors. However, naked mole-rats are an exception: they have an altered ion channel in their pain receptors that is inactivated by acid and makes the animals insensitive to this type of pain. Dr. Ewan St. John Smith and Professor Gary Lewin conclude that this pain insensitivity is due to the African mole-rats' adaptation to their extreme habitat over the course of evolution (Science , Vol. 334, Dec.16, 2011, 1557-1560)*.

The Nav1.7 sodium ion channel plays a key role in the transmission of painful stimuli to the brain. It triggers a nerve impulse (action potential) in the pain receptors sensory nerve cells, the endings of which are found in the skin and which transmit pain signals to the brain. Dentists already use sodium ion channel blockers in the form of local anesthetics, but these target all sodium ion channels they come into contact with, not just the Nav1.7 ion channel. People with defective Nav1.7 ion channels due to a genetic mutation feel no pain, but for them, pain insensitivity is not at all an advantage: minor injuries or infections can go unnoticed, often with serious consequences.

However, this is different for the African naked mole-rat. For these animals, pain insensitivity to acid is evidently a survival advantage. The air in the burrows has such high CO2 levels that humans or other mammals could hardly survive in such an environment. Normally, high CO2 levels and acid cause painful burns and trigger inflammation in all mammals, including humans. Thus, the tissue of patients with inflammatory joint diseases such as rheumatism contains high concentrations of acid. These high acid levels in the tissue activate the pain sensors.

Naked mole-rats also have pain sensors. In a previous study, the research group of Professor Lewin already showed that naked mole-rats are just as sensitive to heat and pressure as mice are. In contrast, they do not feel any pain when they are exposed to acid. Moreover, as Dr. St. John Smith and Professor Lewin report in the American journal Science, naked mole-rats also have the Nav1.7 ion channel like other mammals, including mice and humans. The researchers therefore investigated the function of this ion channel in naked mole-rat and in mouse sensory nerves to determine whether there is a difference between the two species in the function of this ion channel.

In the present study the researchers showed that the NaV1.7 ion channel of the naked mole-rat does in fact differ in structure from that of the mouse or of humans. Ion channels are proteins composed of amino acids, the blueprint of which is coded by the genes. In the NaV1.7 ion channel of the naked mole-rat, three amino acid building blocks are different from those in all other mammals. These three altered protein subunits lead to profound impairment or blockage of the naked mole-rat ion channel by acid. This phenomenon can also be observed in the Nav1.7 ion channel of mice and humans, but it is so weak that the transmission of pain signals is hardly disturbed.

In the naked mole-rat, however, this mutated ion channel is sufficient to inhibit signal transduction. The reason for the mutation in the ion channel, according to the researchers, is that naked mole-rats have adapted over the course of evolution to the high CO2 levels in the air and thus have become insensitive to pain induced by acid. This is also the case when in the nerve cells of the naked mole-rats other ion channels are activated by acid stimuli that would normally activate pain receptors.

Cave-roosting microbats and tree-roosting megabats

In a number of mammals the structure of the gene for the Nav1.7 ion channel has been decoded. These include the cave-roosting microbat (Myotis lucifigus), a bat that lives in a similar habitat and exhibits a similar gene variant. In contrast, another species, the tree-roosting megabat (Pteropus vampyrus), also lives in large colonies like the mole-rat and the cave-roosting microbat, but it is not under any CO2 pressure. According to the researchers, this suggests that under similar environmental conditions in the course of evolution, unrelated species develop similar traits. For the African naked mole-rat, and perhaps for the cave-roosting microbat, this means that CO2 and acid cannot induce pain.

Significance for patients with inflammatory diseases?

What do the findings of the MDC researchers mean for patients with inflammatory diseases, in whom this ion channel is continuously activated? According to Professor Lewin, the pharmaceutical industry is already working to develop small molecules that will block this ion channel. The findings from the laboratory of Professor Lewin that three altered protein subunits inhibit the signal transduction of Nav1.7 may aid the development of small molecules that specifically block this mutated ion channel.

Helmholtz Association of German Research Centres

Related medicine news :

1. IU researchers: Chemotherapy alters brain tissue in breast cancer patients
2. Ben-Gurion U. researchers: High resistance rates among acute otitis media pathogens in children
3. Researchers: Pay more attention to epilepsy
4. Researchers: Elderly patients 4 times more likely to die from treatment complications
5. Researchers: Sexually active teens need confidential health care
6. Wistar researchers: Direct proof of how T cells stay in standby mode
7. Mayo researchers: Genetic mutation linked to Parkinsons disease
8. New Report: The Internet Has More Influence Over Consumer Health Actions than Traditional DTC Channels
9. Father Channels His Grief into Advocacy, Promotes Simple Actions to Make Hospitals Safer for Children
10. 29 Clear Channel stations Nationwide Raise Nearly $2.8 Million to Help Save the Lives of Kids Fighting Cancer and Other Deadly Diseases
11. Lakeside Medical Group, Heritage Provider Network, CEO Dr. Richard Merkin, Featured on Several Segments of Fox National News and Fox Business Channel on Current Healthcare Payment Structures to Physicians
Post Your Comments:
(Date:11/27/2015)... , ... November 27, 2015 , ... ... the toilets were," said an inventor from Hillside, N.J. "Many people catch diseases ... cover so that individuals will always be protected from germs." , He developed ...
(Date:11/27/2015)... ... November 27, 2015 , ... ProSidebar: Fashion is ... Pro X. With ProSidebar: Fasion, video editors can easily add an informative sidebar ... minimalist title opener. Utilize presets featuring self-animating drop zones, lines, bars, and text ...
(Date:11/27/2015)... ... November 27, 2015 , ... ... well-respected Microsoft Dynamics SL User Group (MSDSLUG). Recognized as Microsoft’s official group for ... of Microsoft Dynamics SL software users, partners, industry experts and representatives. Intellitec Solutions’ ...
(Date:11/27/2015)... ... 27, 2015 , ... Keeping in mind challenges faced by ... wellness consultation, has collaborated with a leading web-based marketplace for extra-curricular activities for ... parents and bring advice from parenting experts within their reach. As a part ...
(Date:11/27/2015)... ... November 27, 2015 , ... Dr. Thomas Dunlap and ... and Dr. Tucker Bierbaum with Emergency Medicine at St., Joseph Health System’s Santa ... and Sepsis conditions present in similar ways and require time-critical intervention to avoid large ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... 2015 ) ... "Radioimmunoassay Market by Type (Reagents & Kits, ... Clinical Diagnostic Labs), Application (Research, Clinical Diagnostics), ... report to their offering. --> ... of the "Radioimmunoassay Market by Type ...
(Date:11/25/2015)... 25, 2015 ... the "Global Brain Monitoring Devices Market ... --> ) has announced the ... Devices Market 2015-2019" report to their ... ( ) has announced the addition ...
(Date:11/25/2015)... 2015  Amgen (NASDAQ: AMGN ) today announced ... the United States (U.S.) Food ... candidate to Humira ® (adalimumab). Amgen believes this ... the FDA and represents Amgen,s first BLA submission using ... , M.D., executive vice president of Research and Development ...
Breaking Medicine Technology: