Spicy research may cure pain

Treatment could be better than morphine with a little help from redhot
chiles and other foods that deaden nerves

BY JIM PUZZANGHERA

Mercury News Staff Writer

The substance that sets your mouth ablaze when eating hot peppers flips the
same chemical switch that causes you to feel pain when you touch something
hot. And the discovery of that mechanism could lead to powerful new drugs
to combat all kinds of pain.

In groundbreaking research from the University of CaliforniaSan Francisco
published today in Nature, scientists announced they have cloned a receptor
in the nervous system that tells the brain you're in pain when you torch
your taste buds with jalapeños or singe your skin with scalding water.

The finding is being compared to the discovery of morphine earlier this
century for its potential significance in dealing with pain. But unlike
morphine, which has tremendous drawbacks, such as disorientation and
addiction, this new protein could spawn drugs that turn off pain at the
molecular level without harmful side effects, experts said.

``The community of pain researchers has been waiting with bated breath for
this receptor for . . . the past decade . . . and the reason is this could
be the pain protein,'' said Mary Garry, an assistant professor in the
department of anesthesiology and pain management at the University of Texas
Southwestern Medical Center in Dallas.

``If they do have what they think they have,'' she said, ``it's an
incredibly significant find.''

The discovery stems from something scientists and chefs have known for
years: A substance called capsaicin found in peppers causes a burning
sensation in the mouth.

Capsaicin is so powerful that one ounce of it in 7,800 gallons of water can
be detected by the human tongue. At the turn of the century, a Detroit
pharmacist named Wilbur Scoville extracted capsaicin and created a scale
for measuring the potency of peppers based on taste mild poblano verdes
rate about 1,000 ``Scoville units,'' while habaneros measure 100,000 units.
Pure capsaicin rates 10 million units.

David Julius, associate professor of cellular and molecular pharmacology at
UCSF and lead author of the new research, turned to capsaicin as part of
his lab's study of pain.

``When you eat it, it's not a taste response, it's a stimulation of the
sensory nerve endings that feel pain,'' he said.

Julius and his team believed that if they could track capsaicin through the
body to see how it causes the sensation of burning pain, it could lead them
to a chemical involved in other kinds of pain.

They used capsaicin to narrow down the 2 million to 3 million genes that
are turned on in painsensing cells to find the ones that reacted to
capsaicin. They hit on the gene for a protein called VR1, which acts as a
receptor on the outside of the painsensing cells. When capsaicin hits the
receptor, it essentially turns the cell on, causing a pain signal to be
sent to the brain.

Julius and his team ground up different peppers and mixed them with cells
that contained VR1 in their lab. The hotter the pepper on Scoville's scale,
the more reaction they got from the receptors, he said. And they also found
that temperatures hot enough to cause pain in humans caused similar
responses from the cells with VR1.

``Interestingly, the VR1 channel also senses temperature levels that
produce pain, providing a plausible molecular explanation for why we
perceive food that contains capsaicin as hot,'' David Clapham of Harvard
Medical School wrote in Nature, which put the research on its cover.

In fact, pepper plants probably have evolved the use of capsaicin over time
as a protection against being eaten by humans and animals, Julius said.
Squirrels and other animals usually won't eat hot peppers because of the
burning sensation.

``The plants have taken advantage of the fact that we have this (VR1)
protein by making a substance that says `don't eat me,' '' Julius said.
``Unfortunately for the plant, we have learned to appreciate that substance.''

At UCSF, a member of Julius' team, postdoctoral researcher Michael Caterina
also found that substances released by cells when tissue in the body is
injured, such as being hit hard enough to cause a bruise, amplified the
affect of capsaicin on the receptor. That finding hints that VR1 might also
be involved in that type of pain as well.

The researchers also found that after the initial reaction of painsensing
cells to capsaicin, more of the substance deadens the cell. Clapham
speculated that might be the reason some people become less sensitive to
foods laced with hot pepper the more they eat them.

That deadening of painsensing cells is where the discovery of VR1 could
lead to new drugs for people with chronic pain, Julius said. Already, some
ointments contain capsaicin to ease the pain of conditions like rheumatoid
arthritis.

``It would be nice to develop drugs that skip the part of inducing the
first phase of pain and go right to the part where you take the nerve cell
out of commission for a while,'' Julius said.

Garry said the potential is great.

``We can now manipulate this receptor, insert this into various cell types
and have our way with this receptor to understand what makes pain fibers
tick,'' she said.

And because the receptor is so specific, new drugs could target pain
without affecting other nervous system functions, Garry said.