As mammals go, naked mole rats are one of the strangest. They are exceptionally long-lived and never get cancer, making them very useful for medical research
. Now the secret behind another naked mole rat trait ? feeling no pain from acid ? could help tackle the pain of arthritis.
In most animals, exposure to acid stimulates special channels at the tips of sensory neurons called nociceptors. Ewan Smith and colleagues at the Max-Delbr?ck Center for Molecular Medicine in Berlin, Germany, suspected that these channels behave differently in mole rats.
They were wrong. In both naked mole rats and mice, acid activated the channels. "We found the responses to be largely similar," says Smith.
Stop the pain signal
So the team turned to a different type of sodium channel, called NaV1.7. Also found in nociceptors, these channels become blocked when exposed to acid, stopping the pain signal.
The researchers doused nociceptors from naked mole rats and mice in acid, and found the strength of the pain signal passing through the NaV1.7 channels dropped by 42 per cent in mice, but by 63 per cent in the mole rats.
Smith says there is a balance between the acid-sensing channels that transmit the signal and the NaV1.7 channels that block it. In mice, the balance tips in favour of the acid signal making it to the brain ? but in naked mole rats the balance tips the other way and the pain signal dissipates. "The acid block of NaV1.7 is so strong that the simultaneous activation of acid sensors is irrelevant and no signal is conducted," says Smith.
The team sequenced the gene that codes for the NaV1.7 channel in mole rats, and compared it with SCN9A ? a key gene in the human version of the channel. Humans with mutations to this gene are completely insensitive to pain.
The main difference between the two genes was in a triplet of amino acids that plays a role in determining exactly what acid concentration opens or closes the channel. Smith inserted the mole rat amino acid triplet into the human SCN9A gene, and poured acid over the resulting mutant channel. "Introducing this small sequence resulted in a significantly stronger inhibition of the sodium channel," says Smith.
Arthritis acid
That suggests that this sodium channel could be a target for the development of drugs to prevent the pain caused by acid build-up ? which happens in arthritis and other inflammatory disorders.
Mark Connor at Macquarie University in Sydney, Australia, who was not involved in the study, agrees. "You could potentially develop a drug to bind to that site and reduce its activity to make people less sensitive to pain."
Connor says it's unlikely this is the only painkilling trick up the mole rat's sleeve. They are also insensitive to pain from capsaicin, the essence of chilli pepper. "But capsaicin doesn't affect these sodium channels," he says. He thinks mole rats' nerves may be wired differently to other animals, somehow stifling the pain message.
Journal reference: Science: DOI 10.1126/science.1213760
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