How Naked Mole Rats Beat Chili Pepper Heat

Scientists unlock the secrets to how the critters endure painful stimuli.

ByDan Childs<br>abc News Medical Unit
January 08, 2009, 12:09 AM

Jan. 30, 2008&#151; -- Baby naked mole rats are puny, bluish-pink and -- as their name implies -- utterly without fur.

Place them in your hand, and it's as if your palm has sprouted a new, squirming set of bruised fingers. Put them on a platter, and they resemble cocktail weenies without the toothpicks.

Cute they are not. But some pain researchers might tell you that the tiny, buck-toothed visage of this creature may one day be the face of future advancements in pain management.

So suggests University of Illinois at Chicago researcher Thomas Park. A professor of biological sciences at the university, Park was also lead investigator of a study that revealed the curious adaptations of naked mole rats that altered the way they experience pain. This research was published Tuesday in the journal PLoS Biology.

In short, the rodents seem to be as sensitive to pinching, poking and burning as other mammals are. But when it comes to exposure to acid and capsaicin -- the chemical that gives a spicy, stinging kick to jalapenos and pepper spray -- the naked mole rats are the tiny Bruce Willises of the animal kingdom. They simply don't seem to feel the pain.

"When we applied these substances, there was absolutely no response," Park says. "They completely didn't care."

The research may go further than just shedding light on these denizens of the dark, who spend most of their lives underground, huddled by the hundreds in an area the size of your average shoe box.

Indeed, one of the chemicals of special interest in the findings -- a neurotransmitter known as substance P -- is a common component of pain responses in nearly every mammal, including humans.

"This is the same substance P that, in humans, goes crazy when you have some long-term type of injury that involves chronic pain or inflammation, such as a pulled muscle or post-surgical pain," Park says.

But could the findings in these odd creatures actually have implications for pain in humans? Dr. Doris Cope, a professor and vice chairman of pain medicine at the University of Pittsburgh Medical Center Pain Medicine Program, says that new findings on the way substance P works actually might lead to new approaches for certain types of pain.

The human experience of pain, she says, "is a whole chemical, neurological, biological soup. And substance P is one of the modulators that, in chronic pain, is elevated.

"If you could block substance P or somehow change how it works, it would stop a lot of the signal amplification that goes along with chronic pain," Cope adds.

Indeed, most researchers agree that there is a gulf of difference between the way that animals experience pain and the way a human does. But there are some biological similarities in the pathways by which pain messages are sent to the brain. And substance P is one of them.

In fact, researchers have known about substance P since the 1930s. But until Park and his team found that naked mole rats tested negative for this neurotransmitter in their skin -- and are hence blissfully unacquainted with certain types of pain -- it was commonly assumed that all mammals had this chemical.

"Substance P had been found in the skin of all of the mammals we had ever tested," Park says. "Our first thought was 'we screwed up.'"

When the researchers found that these rodents truly lacked this neurotransmitter -- and hence lacked the normal reaction to certain pain stimuli -- Park consulted a colleague whose expertise lay in genetics.

Exploiting a cold sore virus as a genetic ferry of sorts, the researchers tweaked the germ to carry a bit of DNA into the naked mole rats that would cause their nerves to produce substance P.

"To our shock and amazement, it worked," Park says. The naked mole rats with the genetic tweak now responded to capsaicin."

However, they were still immune to the painful sting of acid. Park and his team dug further, and what they found was that the naked mole rats' lack of substance P was only one of three adaptations that affected the way the critters sense painful stimuli.

Park says that he is hopeful the findings on naked mole rats could one day help scientists devise new ways to temper the suffering of people who battle chronic pain.

"If we can take an animal system like this and figure out they manage to modulate their experience of pain, I think it would be a giant opportunity to find out more about how we can modify pain in humans," Park says.

But as with many biological systems, cutting people's pain experience by meddling with substance P is much more difficult than it sounds. Several drug companies, including pharmaceutical giant Merck, have tried to come up with ways to block substance P to control pain. So far, the results have been mediocre at best.

One of these hopefuls, Cope says, was actually capsaicin itself. Drug developers discovered that putting the capsaicin extracted from hot chili peppers onto a painful site caused the nerve tissues to release all of their substance P in one huge gush. Once the substance P had been drained from the area, the cycle of pain was broken, at least for a while.

But there was a catch, Cope notes. It seems few people are eager to rub capsaicin onto an area of their body that already hurts.

"This is not a treatment that people are compliant with," she says. "Though it may help with chronic pain in the longer term, for the short term people did not want to make the pain worse."

Plus, as the old saying goes, Mother Nature is a miser. In short, few substances in the body do just one thing, and substance P is no exception. Park says the chemical appears so far to be involved in the function of the brain and spinal cord. So blocking it wholesale may not be a viable solution.

"It goes to show that the pain system is super complicated," Park says.

But Cope says this findings, like other advancements in pain research, are useful in assembling the jigsaw puzzle pieces of data that come together to form a greater understanding of why, exactly, we hurt the way we do.

And why, when it comes to certain types of pain, we're somewhat less macho than the average naked mole rat.

"People maybe 30 years ago thought of pain as just a symptom," Cope says. "Now we know there are different types of pain. And at some point, we may have better diagnostics and tailored treatments for different kinds of pain."

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