BioEd Online

Researchers have added to the list of biological curiosities about mole-rats: the animals do not feel all types of pain. The discovery could eventually help humans who are battling chronic discomfort.

African naked mole-rats (Heterocephalus glaber) are unusual creatures — they are cold-blooded mammals, have a long lifespan, and live in co-operative societies of hundreds of individuals in a manner more typical of bees and wasps than moles or rats.

The animals react normally to the mechanical pain caused by pinching and prodding, but are insensitive to a suite of other normally nasty stimuli, according to Thomas Park of the University of Illinois at Chicago, Gary Lewin at the Max-Delbrück Center for Molecular Medicine in Berlin, Germany, and their colleagues.

Those stimuli include acid and capsaicin, the ingredient in chilli peppers that causes a burning sensation in many animals. These mole-rats are also odd in that their skin, when inflamed, does not become hypersensitive when exposed to unpleasantly hot objects, even though they react to excessive heat in the same way that other mammals do, the researchers report in PloS Biology¹.

Sore problem

The team's discoveries began accidentally five years ago, when a neurology experiment revealed that mole-rats lack substance P, a compound that passes signals between nerve cells to convey information about chronic pain. This suggested that chronic pain signals heading to the mole-rat’s central nervous system are much weaker than those in other animals.

The researchers performed a battery of pain tests on anaesthetized mole-rats, and investigated the creatures’ neuroanatomy. They also took independent patches of skin samples with nerves attached to test their responses to acid.

“Instead of going to the pain region of the spinal cord as we would expect, the nerves that lead from acid and capsaicin sensors go to the touch region,” says Park. “And their nerve fibres do not respond to acid at all.”

Gene therapy

To prove the importance of substance P, the researchers rubbed a serum containing a herpes virus that can make cells manufacture substance P into one hind leg of each mole-rat.

This caused the mole-rats to feel the unpleasant burning of capsaicin on that foot. But they still could not detect acid, which suggests that the animals are insensitive to acidic compounds because of some other mechanism.

This might be an adaptation the mole-rats arrived at because of their subterranean home, says Park. “We know that the carbon dioxide levels in mole-rat tunnels are about 2%, and believe those levels could reach 10% in the group areas.” At such concentrations, carbon dioxide would form carbonic acid on the damp membranes of the respiratory system.

Such sturdy insensitivity to acid could turn up new details about how humans experience chronic pain.

Patients with rheumatoid arthritis have joint fluid that is slightly acid, but the contribution of this acid to their chronic pain is unknown, says Lewin. Given that mole-rats may get arthritis but are not bothered by acid, they could be the perfect creatures to answer that question.