[CH] A pucker medical report
Andrew Healy (a.healy@surrey.ac.uk)
Thu, 13 Jul 2000 13:39:17 +0100
Understanding Reactions To Hot Peppers and Baths Could Help Pain Management
SAN FRANCISCO, CA. -- October 22, 1997 -- Researchers at the University of
California San Francisco have identified a molecular key that sensitizes
people to both spicy cuisine and painfully hot temperatures.
The discovery, reported by UCSF researchers led by David Julius, PhD, and
postdoctoral student Michael J. Caterina, MD, PhD, in tomorrow's issue of
Nature, should lead to new knowledge about pain and pain relief, they say,
as well as to better medications for certain pain syndromes. Some of these
chronic pains are already treated with the hot pepper molecule, capsaicin.
The findings might also prove important in developing a better
understanding of unusual genetic disorders in which individuals fail to
experience pain normally and injure themselves unwittingly and
often dangerously as a result.
At the level of molecules and cells, the UCSF researchers have confirmed
the appropriateness of our perception that the chili's spiciness is, in a
sense, hot. The key is one particular protein, a kind of gateway into
pain-sensing nerve cells that opens when it comes into contact with capsaicin.
The protein, called a vanilloid receptor, is responsible for the spicy
sensation that causes the too-hot pepper eater to beeline for the water
pitcher and also for the sensation that a too-hot water bath is painful.
"In the same way that the study of morphine led to the discovery of nerve
pathways in the brain that suppress pain, we believe that our having found
the target of capsaicin activity will illuminate fundamental mechanisms of
pain production," said Julius, an associate professor of cellular and
molecular pharmacology at UCSF.
With prolonged exposure to capsaicin, sensory nerves lose their
responsiveness.
"This phenomenon of desensitization underlies the seemingly paradoxical use
of capsaicin as a painkiller for treating disorders ranging from diabetic
neuropathies to rheumatoid arthritis," Julius said. The long-term loss of
sensitivity to capsaicin is thought to be associated with death or damage
to the nerve cells, he adds.
The cellular target of capsaicin is a receptor molecule scatteredabout the
surface of certain sensory nerve cells, called nociceptors. The receptor
acts as a protein gateway into the cell. The gateway opens in response to
capsaicin to allow positively charged molecules such as calcium to rush
into the nerve cell. This event leads to the electrical transmission of a
pain signal to the next nerve cell in the pain pathway to the brain.
In the early 20th century, a scientist used humans as guinea pigs to
establish his own kind of Richter scale to gauge the relative strengths of
hot peppers. However, Julius and Caterina singed no tongues to make their
discoveries. Their studies did involve a trip to the market for a sampling
of the chili cornucopia, but they did not eat the chilies in the name of
science. Instead they used the peppers in a series of elegant laboratory
studies to confirm that the receptor is a vital sentinel for the detection
of dangerous heat.
The relative pungencies of the store-bought peppers were measured by a
researcher named Wilbur Scoville in 1912. The mild poblano verde used to
make chili rellenos rates about 1,000 Scoville units,
for example, while the fiery orange habanero chili rates 100,000 Scoville
units.
These pain ratings were earlier found to correspond to capsaicin
content,and Caterina has now shown the rated potencies correspond to the
strength of cellular responses to capsaicin, highlighting the importance of
vanilloid receptors in pain signaling. Hot temperatures in the range known
to cause pain in humans elicited similar responses from the
receptor-harboring cells.
Caterina was able to determine cell death appeared to result from the
opening of the receptor gates in response to a large dose of capsaicin.
These results and similar studies that Julius is now conducting may prove
useful in probing new and potentially better drugs that would kill pain
signals transmitted through the vanilloid receptor without harming
neighboring cells, Julius explained.
Often the identification and description of receptors on cells leads to the
discovery of naturally occurring molecules that attach to the receptors and
help to bring about an important physiological change. But so far no
naturally occurring capsaicin-like molecule, or vanilloid, has been
identified that binds to the vanilloid receptor.
However, in the laboratory Caterina found protons -- positively-charged
hydrogen atoms released by cells in response to tissue injury as part of an
inflammatory response -- amplified the effect of capsaicin on the receptor.
This result suggests the vanilloid receptor might play a role in
registering the pain of any injury that results in inflammation. So, this
same population of sensory nerve cells might respond to bruising blows as
well as to caustic chemicals and burning heat, the researchers said.
"I can resist anything, but, temptation" <Oscar Wilde>
That which doesn't kill us, makes us strong ! <Nietzsche>
Andrew Healy