What Rufus (The Naked Mole Rat) Can Teach Us About Pain

On December 25, I posted a piece about pain management and the role of strong narcotics such as fentanyl. One of the points I wanted to make was that there are different types of pain, primarily neuropathic pain and inflammatory pain. In managing patients with cancer pain (or any type of chronic pain, for that matter), it is critical to distinguish between these types of pain, because they respond to different classes of drugs. A paper published today in an online peer-reviewed journal called PLoS Biology reports that a particular animal is insensitive to inflammatory pain.

What animal, you ask? The African naked mole-rat (Heterocephalus glaber).

It turns out that naked mole-rats do not have the pain-related neuropeptide Substance P in the nerves in their skin, which means they cannot feel any inflammatory pain. Scientists tested this in a variety of ways, including injecting very small amounts of either dilute acid (about the strength of lemon juice) or capsaicin (the substance that makes hot peppers “hot”) into their paws. They did not react. To prove that Substance P is necessary and sufficient for the animals to feel pain, the scientists replaced the gene for Substance P in the nerves to one paw, leaving the other 3 alone. In animals treated in this way, injections of capsaicin into the paw with Substance P caused the animals to withdraw and lick their paws, while the mole-rats did not respond to injections into the other 3 paws.

Why is this an important experiment? According to the lead author on the study, "This is important specifically to the long-term, secondary-order inflammatory pain. It's the pain that can last for hours or days when you pull a muscle or have a surgical procedure…We're learning which nerve fibers are important for which kinds of pain, so we'll be able to develop new strategies and targets." Added his supervisor, "We really do not understand the molecular mechanism of acid sensing in humans, although it is thought to be pretty important in inflammatory pain. An animal that naturally lacks such a mechanism may help us identify what the mechanism actually is."

What else do we know about naked mole-rats? Well, these fascinating creatures live in oxygen-starved burrows 6 feet under the ground in East Africa. They are the only cold-blooded mammals. And… some of them can become martial arts masters.



Also, naked mole-rats are an important tool in the study of human aging.

In all seriousness, this is just another example of how science, driven only by curiosity (and not by policy), can lead to unexpected, yet fascinating and ultimately extremely important findings. The best example of that is the discovery of bacteria that live in heated vents on the ocean floor. These bacteria are the original source of the heat-stable Taq DNA polymerase, without which PCR (one of the most important laboratory techniques in molecular biology today) would be impossible.

So the next time you hear about research that on its surface sounds silly, please try to keep an open mind, knowing that important findings sometimes come from the most unexpected places.

I leave you with that thought, and this song: