Why spicy foods burn the mouth.
IN SEEKING TO COMPOSE a perfectly balanced and flavorful dish, the cook naturally looks to old recipes for ingredients whose combination has been tested and validated over the course of centuries. But traditional ways are not always the best. The various elements assembled from culinary experience must harmoniously stimulate not only the senses of taste and smell but also thermal and mechanical sensors, to say nothing of the chemical sensors for spiciness.
Our chances of success will improve if we have a precise understanding of the underlying molecular mechanisms. We know that sour and bitter tastes are offset by sweet ones and that salt facilitates the perception of other tastes, but the molecular basis of the physiology of taste remains incomplete. For example, why do hot peppers of the Capsicum family set the mouth on fire? Why are people who regularly eat hot peppers able to tolerate doses that novices find intolerable? Why do we like to eat foods that cause us pain? David Julius and his colleagues in the School of Medicine at the University of California, San Francisco (UCSF), cast light on these questions by studying the receptor for capsaicin, the active principle in chili peppers, paprika, and cayenne.
Pain and the Brain
An important advance in human physiology was made several decades ago with the exploration of the effects of morphine on the brain and the identification of the receptors for morphine and its derivatives. If an organism contains such receptors, researchers reasoned, molecules analogous to morphine ought to be able to be found in the body. This assumption turned out to be correct: Endogenous opioids were soon discovered, along with the regulatory system for suppressing pain.
Julius and his colleagues reasoned in a similar fashion that if our species consumes spicy foods whose molecules activate pain pathways, evolution ought to have endowed the human organism with receptors for endogenous molecules involved in signaling pain.
How to go about identifying these receptors? The UCSF biologists first isolated the RNA messengers present in the neurons that detect spiciness in the mouth and synthesized a group of corresponding DNA molecules. They then introduced these molecules in various cell cultures to observe the bonding between capsaicin and the proteins produced by the inserted DNA. Finally, they identified the DNA that codes for the receptor of capsaicin, known as VRI. Introducing this DNA sample in frogs’ eggs yielded cell cultures whose membrane contained the desired receptor. Further analysis established that VRI is a membrane channel protein, which regulates the passage of ions (above all calcium ions) between the outside and inside of cells. It was also shown that VRI has four subunits and that binding with capsaicin opens the channel.
What value do these studies have for gastronomy? Earlier psychophysiological research had led American chemist Wilbur Scoville in 1912 to devise a sort of Richter scale for heat that now bears his name. The electrophysiological recordings of frogs’ egg cells equipped with the VRI receptor demonstrated the soundness of this classification: The cellular response (and therefore, presumably, the neuronal response in the brain) turned out to be proportional to the concentration of capsaicin.
Julius and his colleagues showed that capsaicin, which is fat soluble, can bind itself to the VRI channel, either on the surface of nerve cells or inside them. Its affinity for fatty substances explains why drinking water does not put out the fire in the mouth, but eating bread does.
Acclimatization to Spices
Exposing the receptors to capsaicin yielded additional information about acclimatization to spicy dishes. The opening of the VRI channel triggers the inflow of calcium ions into the neuron, which emits a nerve impulse when the intracellular electrical potential reaches a certain threshold. Nonetheless, an upper limit appears to exist as well: Frogs’ egg cells equipped with the VRI receptor die after a few hours of continuous exposure to capsaicin, evidently because the inflow of calcium ions is excessive.
The loss of sensitivity observed in spice lovers seems to result from the death of sensory fibers. This would explain the paradoxically analgesic effect of capsaicin in the treatment of viral and diabetic neuropathies and of rheumatoid arthritis, where by killing pain neurons it helps reduce the sensation of pain.
Finally, the UCSF team showed that rapid increases in temperature trigger ion currents in the VRI receptor analogous to the currents triggered by capsaicin. The VRI channel therefore turns out to be both a chemical and a thermal sensor, which is why eating spicy dishes makes the mouth feel as though it is on fire.