Living without Pain – The African Naked Mole-Rat

“Acid and Chili Peppers Produce no Pain – Researchers attribute Pain Insensitivity to Selection Pressure Arising from an Extreme Habitat”

The African naked mole-rat (Heterocephalus glaber) is one of the most unusual mammals. It is only 15 centimeters long, lives in subterranean colonies of up to 300 individuals in arid areas in central East Africa, and it feels no pain.

Professor Gary R. Lewin from the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, and Professor Thomas J. Park from the University of Illinois at Chicago, USA, took a closer look at this strange rodent. They could show, that the animal is absolutely insensitive to acid. “This is completely unique in vertebrates”, says Professor Lewin. Also, it lost its sensitivity to capsaicin, the hot substance in chilli peppers which normally causes a burning sensation when applied to the skin.

The researchers conclude that the extreme native habitat of the African naked mole-rat may have triggered this unique pain insensitivity.

The African naked mole-rat (Heterocephalus glabor) is one of the world's most unusual mammal. One of its many striking features is, that it feels no pain. (Photograph: Ewan St. J. Smith/ Copyright: MDC)

Pain Receptors

In earlier research Professor Park found that African naked mole-rats naturally lack certain substances, substance P and calcitonin gene-related peptide (CGRP), which are involved in the transmission of pain signals to the brain,. But this lack did not explain why these animals are insensitive to pain. These findings therefore prompted Professor Park and Professor Lewin to undertake a systematic anatomical, behavioural and physiological analysis of the sensation of pain, nociception, in these animals.

Like all vertebrates the African naked mole-rat does have pain receptors which researchers refer to as nociceptors. Nociceptors are sensory neurons that can sense stimuli that give rise to pain. Their endings in the skin normally respond to potentially damaging stimuli and send these signals to the brain, which is necessary for animals to avoid dangerous situations.

Acid usually is very noxious and painful to all mammals including man, and vertebrates, including amphibians and fish. In African naked mole-rats the situation is radically different. It is the only vertebrate, which does not react to any acidic stimulus at all. The pain researchers in Berlin and Chicago could show, that the nociceptors in naked mole rat are simply not excited at all when the skin tissue is made acidic. The naked mole rat thus completely lacks the ability to find acid painful.

Vigorous Response to Chili Peppers

In contrast, the African naked mole-rats nociceptors do respond vigorously to capsaicin, the active ingredient in chilli peppers. This substance causes sensation in the mouth when we eat extra hot meals, but at higher doses this substance causes intense pain when applied to the skin. Strikingly, naked mole rats do not react to capsaicin at all. Thus application of high concentrations of capsaicin to the skin provokes no reaction at all.

In this case Professor Lewin and Professor Park could demonstrate that the nociceptors are in fact vigorously activated by this pungent compound in the naked mole rat. This was a paradox as activation of nociceptors usually leads to a behavioural response indicative of some discomfort. The researchers could show that the capsaicin sensitive nociceptors activate regions of the brain that are distinct from those activated by the same neurons in “normal” mammals. They concluded that these pain signals may run into “nowhere” or produce sensations in the naked mole rat that are not unpleasant.

Extreme Habitat

African naked mole-rats live in high density colonies cramped together in narrow underground burrows. There social structure is very akin to that of bees or termites. Oxygen-supply in the burrow system is extremely low, and carbon dioxide levels are so high, that they would be life-threatening for humans. African naked mole rats are also the only known cold-blooded mammal. This means it adjusts its body temperature to its surrounding and cannot generate heat, for example by shivering. Naked mole rats are also extremely long lived, they can live to 25 years old, whereas the natural life span of a mouse is around two years.

The researchers point out, that high levels of carbon dioxide usually constantly stimulate nociceptors because high carbon dioxide leads to tissue acidification. They postulate, that during evolution African naked mole-rats dispensed with acid activation of nociceptors because of high levels of carbon dioxide to ensure the animals fitness for survival. Professor Lewin and Professor Park think that inflammatory pain insensitivity in this mammal could be a by-product of its adaptation to an extreme environment.

Now, Professor Lewin and Professor Park wish to study this pain insensitivity further on a molecular and cellular level. These studies may provide significant insights into the evolution and organization of pain sensing in other mammals including humans.

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Courtesy Max Delbrück Center for Molecular Medicine (MDC)

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