Scientists have learned the secret to pain resistance in mole rats. Opportunity for highly effective painkillers
Cretaceous rodents, which include more than a dozen species found in sub-Saharan Africa, have quite a few unique abilities. One of them is insensitivity to many different types of pain. This is due to subtle differences in gene activity and protein structure. Analysis of these differences could lead to the development of highly effective painkillers.
Cretaceous became notorious in 2008, when Gary Lewin of Max Delbrück Center for Molecular Medicine in Berlin, along with Thomas Park of the University of Illinois at Chicago, published on „PLOS Biology” results of a study in whichorics have reported that these rodents are extremely resistant to bol. The animals were exposed to acid or capsaicin – The compound responsible for the spiciness of chili peppers. This, however, seemed to make no special impression on them.
The researchers established a cooperativeohe teamed up with colleagues from South Africa and Tanzania and continued their research on the astonishing resistance to bol of these rodents, resulting in a new publication, this time in the pages of the „Science”. – Observations, whichore have emerged during studies on these animals should pomoc, among others, in the development of new drugsoin counterbolowe – admitted Lewin.
In a just-published study, the researchers examined how theob Cretaceous and several other related speciesow respond to three substances thatore usually cause a strong burning sensation in humans and other mammalsow. The substances were dilute hydrochloric acid, capsaicin and allyl isothiocyanate (AITC). AITC is what gives horseradish or wasabi its uniquely pungent flavor. These rodents are exposed to these and similar substances in the wild.
The study showed that three species of mole-rats were found to be insensitive to acid. Two species did not show symptomoin bolu after injecting a capsaicin solution into the pawpaw. – Others on the crotko raised their paw or licked it, indicating that these animals felt the krotic feeling bolu,” explained Lewin.
Only one species has proved resistant to AITC – the Hotentock’s earthworm (Cryptomys hottentotus pretoriae) named after a region in eastern South Africa in which theorym occurs. – It was an exciting discovery for us. AITC attacks amino acids in the body and can thusob destroy proteins – explained Lewin.
To uncover the molecular reasons for these rodents’ unusual resistance to bol, the scientists collected from all the species studiedoin probki tissues from the spinal cord and the ganglia ofoIn the dorsal roots, where clusters of neuronaloin, ktore transmit signals bol to the spinal cord. – Thanks to state-of-the-art sequencing technology, we were able to poroKnow the activity of about 7,000 genesoin this tissue,” said Lewin.
Teamoł quite quickly observed that the activity of dwoch geneow has been altered in animals thatore did not feel the bolu. These genes are related to ion channels (TRPA1 and NaV1.7) and are involved in the perception of bolu.
– AITC and many other factorsoin irritants found in roots, whichore are one of the mainownych sourcesofood of these rodents, activates TRPA1. Therefore, in the course of evolution, many species ofow reduced the level of gene expression for this channel. But „wasabi channel” is the only one thatory was completely turned off in the Earthling Hotentock,” explained Lewin. He and his teamoł have discovered that this is due to a particularolently active gene for another channel – NALCN.
– When we blocked the NALCN channel by administering the drug, the rodent suddenly became sensitive to AITC – said Lewin. But just a day after the antagonist was administered, the animals regained their indifference to the substance. – Of the thousands of genesoIn whichore we looked, we found the gene responsible for the unusual resistance to bol in the Earth’s Hotentock landmass – added Lewin.
– On the practical side, this discovery could lead to the development of highly effective agentsow counterbolowe. This rodent has shown us that high expression of the NALCN channel appears to be a very effective way of alleviating bolu – admitted Lewin.
Resistance to bol has allowed the cretebugs to colonize new habitatoInaccessible to many other speciesow. Someore of them are able to live even alongside painfully biting venomous mrowek. But not only insensitivity to bol amazes in these creatures. In a study published last year in the pages of the „eLIFE” found that the risk of death of golcoin sandfly – A species belonging to the molecule family – does not increase with age, as is the case for every other known mammalian speciesow. For more on this topic, see the text – sand char – a rodent thatory violates the biological law of aging.