Chili peppers are one of the great protagonists of the 2021 Nobel Prizes and, if it had not been for them, perhaps David Julius and Ardem Patapoutian would not have received the 2021 Nobel Prize in Physiology or Medicine thanks to their discoveries about how they start nerve impulses to be able to perceive temperature and pressure .
And what do chili peppers have to do with the above? They have to do a lot, and that is that David Julius used capsaicin , a spicy compound in chili that induces a burning sensation , to identify a sensor in the nerve endings of the skin that responds to heat. Ardem Patapoutian, for his part, used pressure-sensitive cells to discover a new class of sensors that respond to mechanical stimuli in the skin and internal organs. These groundbreaking discoveries began intensive research activities that rapidly increased our understanding of how our nervous system perceives heat, cold, and mechanical stimuli. The laureates have identified critical links that were missing in our understanding of the complex interplay between our senses and the environment. In summary, what these two researchers have discovered is how thermal and mechanical stimuli are converted into electrical impulses in the nervous system .
Capsaicin from chili peppers
In the late 90s, David Julius began experimenting with capsaicin in order to discover how this substance, present in chili peppers, activates nerve cells that cause pain sensations . Contact with peppers was known to cause burning, but not in what way.
Julius and his team created a library of millions of DNA fragments corresponding to genes that are expressed in sensory neurons that can react to pain, heat and touch. The researchers considered including in it a DNA fragment that would encode the protein capable of reacting to capsaicin. They expressed individual genes from this collection in cultured cells that do not normally react to capsaicin. After a painstaking search, a single gene capable of making cells sensitive to capsaicin was identified (Figure 2). The capsaicin gene had been found.
Further experiments revealed that the identified gene encoded a new ion channel protein, and this newly discovered capsaicin receptor was subsequently named TRPV1 . When Julius investigated the protein’s ability to respond to heat, he realized that he had discovered a heat sensing receptor that activated at temperatures perceived as painful (Figure 2).
The discovery of TRPV1 was a breakthrough that paved the way for unraveling other temperature-sensitive receptors. Independently, David Julius and Ardem Patapoutian used the chemical menthol to identify TRPM8, a receptor that was activated by cold . Other ion channels related to TRPV1 and TRPM8 were identified and found to be activated at different temperatures. Many laboratories carried out research programs on the role of these channels in wind chill using genetically engineered mice that lacked these newly discovered genes. The discovery of TRPV1 by David Julius was the breakthrough in understanding how temperature differences can induce electrical signals in the nervous system.
