[tt] [s-t] tweaking genes digest #2

[Eugen Leitl]

[from somelist]

It appears that scientists have taken your naked mole rat recommendations
seriously, and have discovered that they can't be tortured with acid and chili
peppers.

http://news.yahoo.com/s/livescience/20080129/sc_livescience/strangecreatureimmunetopain;_ylt=ApWmleah4zpEVabw0mEZMOMiANEA

It's a good thing they're not cute, or the PETA people would be all over it. Of
course, since it turns out nekkid mole rats are immune, it's not really torture,
is it...

Anne Marie
-- 
Things turn out best for the people who make the best
of the way things turn out.
                                                        -- John Wooden

 Strange Creature Immune to Pain

Charles Q. Choi

As vulnerable as naked mole rats seem, researchers now find the
hairless, bucktoothed rodents are invulnerable to the pain of acid and
the sting of chili peppers.

A better understanding of pain resistance in these sausage-like
creatures could lead to new drugs for people with chronic pain,
scientists added.

Naked mole rats live in cramped, oxygen-starved burrows some six feet
underground in central East Africa. Unusually, they are cold-blooded 
which, as far as anyone knows, is unique among mammals.

"They're the nicest, sweetest animals I've ever worked with  they
look frightening, but they're very gentle," said neurobiologist Thomas
Park at the University of Illinois at Chicago.

Scientists knew the mole rats were quite sensitive to touch  perhaps
to help replace their almost useless eyes. After probing their skin,
Park and his colleagues unexpectedly discovered the rodents lacked the
chemical Substance P, which causes the feeling of burning pain in
mammals.

The researchers discovered that when unconscious mole rats had their
paws injected with a slight dose of acid, "about what you'd experience
with lemon juice," Park said, as well as some capsaicin  the active
ingredient of chili peppers  the rodents showed no pain.

"Their insensitivity to acid was very surprising," Park told
LiveScience. "Every animal tested  from fish, frogs, reptiles, birds
and all other mammals  every animal is sensitive to acid."

To explore their pain resistance further, the researchers used a
modified cold sore virus to carry genes for Substance P to just one
rear foot of each tested rodent. Park and his colleagues found the DNA
restored the naked mole rats' ability to feel the burning sensation
other mammals experience from capsaicin.

"They'd pull their foot back and lick it," Park said. Other feet
remained impervious to the sting of capsaicin.

"Capsaicin is very specific for exciting the fibers that normally have
Substance P," Park added. "They're not the fibers that respond to a
pinprick or pinch, but the ones that respond after an injury or burn
and produce longer-lasting pain."

Curiously, the researchers found that mole rats remained completely
insensitive to acids, even with the Substance P genes. This suggests
there is a fundamental difference in how their nerves respond to such
pain.

"Acid acts on the capsaicin receptor and on another family of
receptors called acid-sensitive ion channels," Park said. "Acid is not
as specific as capsaicin. The mole rat is the only animal that shows
completely no response to acid."

Why so insensitive?

Scientists theorize naked mole rats evolved this insensitivity to acid
due to underground living. The rodents exhale high levels of carbon
dioxide, and in such tight, poorly ventilated spaces it builds up in
tissues, making them more acidic. In response, the mole rats became
desensitized to acid.

"To give you an idea of what they experience, we normally all breathe
in carbon dioxide levels of less than 0.1 percent. If people are
exposed to an air mixture with as low as 5 percent carbon dioxide,
we'll feel a sharp, burning, stinging sensation in our eyes and nose,"
Park said. "We hypothesize that naked mole rats live in up to 10
percent carbon dioxide."

Researcher Gary Lewin, a neuroscientist at the Max Delbr|ck Institute
for Molecular Medicine in Germany, noted, "People may say, 'So what 
it's weird, but what has it to do with human pain?' I think that is
wrong, unimaginative and short sighted."

Lewin noted that all vertebrate pain-receptor systems "are built in a
highly similar way, so the mole rat may tell us how you can unbuild
the system."

Specifically, Park noted this research adds to existing knowledge
about Substance P. "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," he
explained.

As such, these findings might shed new light on chronic pain. Park said,

"We're learning which nerve fibers are important for which kinds of
pain, so we'll be able to develop new strategies and targets."

Lewin added, "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."

Park next plans to study distantly related animals that dwell in
similar circumstances, such as the Mexican free-tailed bat and the
Alaskan marmot, which both spend large amounts of time in high carbon
dioxide caves or burrows. "How are they surviving down there? It'd be
interesting if we saw some parallels there with the naked mole rats,"
Park said.

The scientists detailed their findings online Jan. 28 in the journal
PLoS Biology.

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