The crisp, cooling sensation elicited by menthol has been known since antiquity. According to legend, the Greek god of the underworld, Hades, enraged his wife, Persephone, by having an affair with the nymph, Minthe. Persephone, not inclined to take this transgression lightly, transformed Minthe into an herb. Fortunately, for us, the menthol, which is produced by various mint plants has many beneficial purposes. These include its usefulness not only as a flavoring ingredient but also as a local anesthetic, replacing mild pain as well as the irritation from itching with a pleasant feeling of cool. Despite its ancient origins, until quite recently, the means by which menthol could conjure up the same feeling as low temperature remained a mystery. It turns out that the same protein that is “turned on” by menthol is also turned on by cool temperatures. This protein, called TRPM8, allows calcium and other ions into cells in response to cool temperatures or in response to menthol. So, this longstanding observation now has a “cool” molecular explanation.
Other TRP channels also provide a fascinating explanation for similar long known phenomenon. For example the pungent ingredient in hot chili pepper, capsaicin, elicits the sensation of thermal heat. Capsaicin also has beneficial effects as topical application of capsaicin is a long known remedy to reduce certain forms of pain that arise from conditions such as arthritis, shingles or psoriasis. Another TRP channel, TRPV1, offers a molecular explanation for these observations. TRPV1 is turned on either by capsaicin or by noxious heat. Constant exposure to capsaicin initially turns on TRPV1, but with constant exposure ultimately turns off the channel. Therefore, several large pharmaceutical companies are now searching for drugs to inhibit these channels. If such drugs were identified, they would be very useful in reducing the sensation of certain forms of acute and chronic pain. Interestingly, although humans and other mammals can detect capsaicin, birds do not sense this pungent ingredient. This is why capsaicin is added to bird feeders, since squirrels but not birds are repulsed by this ingredient.
Have you ever considered why your ability to sense “sweetness” in frozen foods, such as ice cream, is enhanced as it melts in your mouth? A third TRP channel, TRPM5, is turned on directly by warm temperatures and indirectly by sugars. Therefore, TRP channels provide a molecular explanation for this long known observation as well. In fact, TRP channels also appear to contribute to the responses to several types of drugs such as nicotine and the active ingredient in marijuana. Therefore, TRP channel have important implications for understanding and possibly treating certain forms of drug addiction.
