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Red Hot Chili Peppers: Feel the Burn

By Nancy Touchette

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Bite into a chili pepper and you’re likely to feel an intense burning sensation—as if your mouth’s on fire. That’s because the protein that detects heat also detects the molecule that puts the “hot” in red hot chili pepper.

One of the hottest. The habañero chili (Capsicum chinense).

Now, a new study helps explain how nerve cells sense heat and chemical irritants such as capsaicin, the active ingredient in hot peppers.

Researchers at the University of California, San Francisco, identified a region of a protein that appears to regulate the temperature at which heat is detected. The protein, a capsaicin receptor, may set the “thermostat” of the nerve cell.

The findings, published in Science, could eventually lead to new drugs to treat chronic pain and may help explain why individuals respond differently to heat and painful stimuli, including hot peppers.

Capsaicin and heat both cause the capsaicin channel to open up. This allows ions to flow through and ultimately send a "hot" signal to the brain.

The capsaicin receptor forms a channel in the membrane of certain nerve cells. The channel is closed unless stimulated by heat or capsaicin; then it opens, allowing ions to flow through. The flowing ions trigger a message that is sent to the brain: “It’s hot!”

The channel responds to temperatures above 43 degrees C (109 degrees F). If the normal threshold for detecting heat were too low, one would feel pain all the time. If it were too high, one wouldn’t respond to harmful heat.

“Nature has designed this channel very carefully,” says David Julius of UCSF, who made the discovery with his colleague Elizabeth D. Prescott. “The channel is activated by heat that can injure.”

At times, such as after bad sunburn, nerve cells may lower the threshold because the body is less able to handle further damage.

The newly identified region binds to a molecule that normally blocks the channel. But enzymes released during inflammation break down the molecule and make the channel more responsive to lower temperatures or less capsaicin.

Understanding the mechanism of the channel could help in developing drugs for chronic pain associated with conditions such as arthritis, shingles and diabetic neuropathy. These conditions are often treated with capsaicin, which is thought to deaden nerve endings.

Julius and his colleagues previously identified a similar channel that responds to cold and chemicals such as menthol. The similarity between the channel proteins may explain why menthol feels cool and peppers feel hot.

Julius has some advice for people who overdo the red hot chili peppers: Drink milk or eat lots of fatty foods. “Fat helps dissolve the capsaicin out of tissues,” he says. “Drinking water when your mouth is on fire spreads the chemical around and makes the situation worse.”

“And don’t stick your finger in your eyes,” he adds.

Prescott, E.D. and Julius, D. A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity. Science 300, 1284-1288 (May 23, 2003).

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