How your harsh reaction to horseradish may lead to new pain-managing medicines


Chili peppers’ punch is an evolved defense mechanism. (bigstockphoto/BIGSTOCKPHOTO)
September 5, 2011

The next time you experience a horseradish rush — you know, those tear-jerking omigod seconds when your entire head is tsunamied by pungency from the too-big dollop of herb you just wolfed down — consider that some biologists describe your moments of agony as nothing less than a brief exposure to a natural form of tear gas.

The horseradish’s primary chemical irritant, allyl isothiocyanate, stimulates the same class of chemical receptors on the same sensory cells in your mouth, throat, nose, sinuses, face and eyes as do tear gas agents and pepper spray’s capsaicin, the chemical in chili peppers that lights your mouth on fire.

In recent years, scientists have been uncovering the biological mechanisms underlying these sensations. They say their discoveries could lead to new pain-managing medicines and provide insights into whether adding menthol to cigarettes makes it easier to get hooked on on them.

But before we go there, it is worth looking at how and why we take notice of such chemicals at all. It comes down to this: Evolution has given animals, including us humans, some serious protective measures against harmful chemicals in the environment. Meanwhile, plants, which have been forced to be sneaky because of their inability to run away, have developed chemical defenses to prevent them from being eaten, at least by animals that don’t help spread the plants’ seeds.

Let’s say you are a horseradish plant and a teeny worm starts biting into the vital flesh of your root. You can’t flee or hide to protect yourself. But, if you were a clever vegetable, you could make sure that the bite would trigger an enzymatic reaction that produces a coercive “DO NOT EAT” command, in the form of allyl isothiocyanate released into that bitten morsel of root. That’s the same tongue-punishing essence in spicy mustard oil.

Horseradish, mustard, wasabi, various peppers, garlic, onion and other vegetables have evolved these chemical-agent defenses in part because animals, meanwhile, evolved an ability to detect and react to chemicals in their environment that can injure or kill. This accounts for our get-it-away-from-my-body responses: rapid-fire sneezing, bronchial pathways clamping shut, coughing spasms and floods of tears. In the context of evolution, vegetables managed to tap into these reactions in animals to increase their own success rate at spreading their seeds. Keep in mind that chili peppers are so clever that their capsaicin fails to repel certain birds that are good at dispersing the chili’s seeds through their excrement.

Pungent foods, tear gas and even mouthwash push on your comfort zone in the same way, by opening the gates on teeny tiny pores — called Transient Receptor Potential (TRP) channels — that are all over sensory cells in your mouth, nose, throat, eyes and face, among other places. When these pores open up, the cells are more likely to send signals to the brain, which then orchestrates the sneezing, coughing, tearing and other chemical-purging behaviors.

“Everywhere you feel pain, that is where [TRP channels] are,” said Sven-Eric Jordt, a pharmacology professor at the Yale School of Medicine.

This makes these receptors alluring to those trying to invent next-generation painkillers.

Jordt has been studying what roles TRP channels play in inflammation, arthritis and other chronically painful conditions.

He also has been looking into a connection with smoking.

“We are finding that menthol can suppress pain and irritant responses to smoke” in the throat and elsewhere, Jordt said. “The menthol enables people to inhale more, so it might help people get hooked.”

He notes that the Family Smoking Prevention and Control Act, signed into law two years ago, gives the Food and Drug Administration authority to ban flavored cigarettes but says menthol was exempted, at least for the time being, partly because the scientific understanding of how menthol interacts with TRP channels remains incomplete.

Jordt also suspects there are connections between asthma and receptor channels designated TRPA1.

“Mice made deficient in TRPA1 channel don’t get asthma,” he notes, adding that these specific channels make for an attractive target for new asthma treatments.

“Fifteen years ago, no one knew what a TRP channel was,” said sensory physiologist Wayne Silver of Wake Forest University in Winston-Salem, N.C. “Now we see them everywhere.”

These receptors make themselves abundantly known to each of us every day.

“My son uses a mouthwash every morning, and every morning he sneezes,” Silver offered as an illustration.

Irritating mouthwash chemicals such as thymol and methyl salicylate trip open two of the almost 30 known TRP channels — TRPA1 and TRPV1. Meanwhile, other mouthwash ingredients, such as eucalyptol and menthol, switch open the TRPM8 channel, which also responds to cold temperatures. In this way, these “cool” chemicals buy time for the more irritating active ingredients to do their mouth washing.

“These receptors have a lot to do with our sense of ourselves inside, and they affect our feelings of pleasure and pain,” said Gina Story, a biomedical scientist at the Washington University Pain Center in St. Louis. She and her colleagues have been investigating differences between the sexes in the distribution of these receptors. Her findings, she said, could end up explaining why “men and women fight over the thermostat.”

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