Biology Question #3873
Brian, a 33 year old male from Denver, CO asks on May 21, 2007,
When eating spicy foods, the tongue and lips can get a burning sensation. Why don't the insides of the cheeks do the same?
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The active chemical compound in chili peppers is capsaicin. It is the active ingredient in “pepper sprays” and is an irritant that produces a sensation of burning on contact. But capsaicin doesn’t really cause chemical burns to the tissues of the eyes and skin; it just induces the sensation of burning. Capsaicin molecules interact with a special nerve receptor in tissues called the vanilloid receptor subtype 1 (TRPV1). This receptor normally responds to the presence of potentially injurious stimuli such as heat, acidic solutions, and a number of other harmful substances or stimuli. When activated, it produces nerve signals perceived by the brain as painful or burning sensations. By binding to the vanilloid receptor, the capsaicin molecule produces the same effect that excessive heat or abrasive damage would cause, which explains why the spiciness of capsaicin-containing foods feels like a burning sensation.
As to why the lips, the tongue, and the inner surface of the cheeks (the “buccal mucosa”) might be differentially sensitive to capsaicin, I couldn’t find the definitive answer, but I can make the following guesses.
It makes sense evolutionarily for mammals to have sensitive lips because this would heighten the probability that an animal would reject a dangerous substance before it even gets into the mouth (where some could be absorbed even if it is not swallowed). The upper lip, the lower lip, and the tissues of the inside of the cheeks are each served by a different branch of the trigeminal nerve. The sensory nerve supply to the tongue is from another cranial nerve altogether. I looked, but I couldn’t find any actual research that said that these different nerve branches are differentially supplied with TRPV1 receptors in their nerve endings, but I’d be willing to bet they are–-that is: the nerve endings of the lips would be more densely packed with these receptors than those that serve the inside of the mouth. Alternatively, the density of the nerve endings themselves could be greater in the lips, which would amount to the same thing as far as sensitivity per unit area of skin surface goes. We do know that the lips are among the most sensitive and discriminative skin surfaces on the body with respect to touch stimuli, so it would make sense that they would be more sensitive to these kinds of pain-inducing stimuli too. That would account for the greater sensory effect of capsaicin on the lips than the inner cheek surfaces. The tongue has lots of heat-sensitive receptors, as well as the sweet/sour/salty/bitter/MSG-sensitive ones that innervate the tastebuds, so it might be more sensitive to capsaicin for that reason.
Also, capsaicin apparently isn’t very water soluble. So, to the extent that the inner cheeks are wetter than the lips most of the time, this might also contribute some to the lesser sensation caused by capsaicin inside the mouth. That wouldn't fit with the tongue being more sensitive, but the tongue is dotted with special receptor cavities right on it's surface, so the receptors come into direct contact with chemical stimuli (as opposed to having to cross membrane barriers first), so that might resolve this apparent paradox. Also, given that the tongue is innervated by different crainal nerves than the lips and inner surface of the cheeks, it may also be more richly supplied with vanilloid receptors. The tongue is often used as an exploratory member, especially in lower animals. Sensitivity to dangerous substances would be a great evolutionary advantage there too.
Finally, I did find some recent research, done at the University of Alberta, that demonstrated different cellular architecture and varying absorption characteristics in the outer cellular layers of different parts of the mucosal tissues inside the mouth region (this is being explored as a possibly useful way of administering certain drugs that might be absorbed through the mucosal skin layers). The epithelium of the buccal mucosa is thicker than that of the sublingual epithelium (under the tongue), for instance. This contributes to their different absorbancy. I didn’t find anything specific to capsaicin absorption in the skin of the lips versus the buccal cavity, but if these skin cell differences made it easier or harder for the molecule to cross the membranes to reach the vanilloid receptors, that could also make their respective regions more or less sensitive to capsaicin. I did find evidence that the mucosal membranes are more absorbent than skin surfaces in general (which would count against my hypothesis), but the anatomical composition and physiological processes of the lips are so different in so many other ways, compared to other parts of the skin, this might not be such a serious drawback for my speculations.
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