The rodent that doesn’t dance to the Red Hot Chili Peppers

Pain begins when damaged cells release molecules that dock onto neighboring nerve cells. This creates an impulse that travels along the cell to its point of contact with pain-receiving nerves in the spinal column, which transmit it on to the brain. To find out why naked mole rats don’t feel pain caused by heat, acid, or capsaicin, the ingredient that makes chili peppers hot, Lewin and his team have been studying every step along the way.

Thomas Park and other members of Lewin’s lab, along with collaborators from the University of Illinois in the US, discovered that there seem to be several reasons for the rodents’ lack of sensitivity. All of them have likely evolved because of the animals’ unusual lifestyle.

The naked mole rat is at home in Central East Africa. As well as being hairless, the animals are blind and virtually deaf. They live underground in colonies of up to 300 animals, nearly always huddled together in a huge cluster that has a social structure like a beehive. One of the females is chosen as queen and two or three males as her mates; the others remain infertile. In the tight space of their burrows, levels of CO₂ rise to high levels that would asphyxiate other animals.

Their insensitivity to pain of acid, heat, and inflammations may all be related to the high CO₂ content of their environment. Breathing high amounts of CO₂ makes body tissues acidic; the same thing happens in inflammation. So the rodents have likely been under strong evolutionary pressure to eliminate mechanisms that cause these types of pain.

Studies of pain molecules, the receptors on nerve cells, and the wiring of the rodents’ nervous system revealed changes at virtually every level of the naked mole rat system for sensing pain. Their cells don’t produce pain-signaling proteins called substance P or CGRP. They do have a protein capable of sensing capsaicin, called TRPV1. Birds can eat peppers and carry their seeds because they have an unusual form of TRPV1 that isn’t triggered by this hot substance. That’s not the case in the naked mole rats; TRPV1 senses it and transmits a signal through the nerve. But it isn’t perceived as pain – nor do the animals become hypersensitive to heat during an inflammation, sensations which are also transmitted through TRVP1.

So where does this insensitivity come from? The new study suggests that connections between nerve cells may be responsible. Pain-sensing nerves are wired into a region of the spinal cord called the dorsal horn. In mice most nerves from the skin make contact with their partners at the border of this region, near the surface. In naked mole rats, most of these contacts happen much deeper. When mice and ​“normal” mammals experience pain, the greatest stimulation of these nerves happens close to the surface. Lewin hypothesizes that balance may be the crucial factor: if nerves at the surface of the dorsal horn do more signaling, information from the skin will be interpreted as pain. If the main stimulus comes from cells deeper in the spine, it will not.

Evolution has interrupted the transmission of pain at several levels in the naked mole rat, from molecules that stimulate nerves to the wiring that sends signals on to the brain. Any of these levels may lead to methods to block pain in humans. Understanding why the naked mole rat doesn’t hurt, Lewin hopes, may reveal why the rest of us do.

- Russ Hodge

Highlight Reference:

Park TJ, Lu Y, Jüttner R, Smith ES, Hu J, Brand A, Wetzel C, Milenkovic N, Erdmann B, Heppenstall PA, Laurito CE, Wilson SP, Lewin GR. Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber). PLoS Biol. 2008 Jan;6(1):e13.

The Wikipedia entry on the naked mole rat
 

Lewin Lab

Molecular Physiology of Somatic Sensation