Our ability to sense heat, cold and touch is essential for survival and underpins our interaction with the world around us. In our daily lives we take these sensations for granted, but how are nerve impulses initiated so that temperature and pressure can be perceived? This question has been solved by this year’s Nobel Prize laureates.

The laureates identified critical missing links in our understanding of the complex interplay between our senses and the environment.

University of California, San Francisco David Julius utilized capsaicin, a pungent compound from chili peppers that induces a burning sensation, to identify a sensor in the nerve endings of the skin that responds to heat. Scripps Research in La Jolla, California scientist Ardem Patapoutian used pressure-sensitive cells to discover a novel class of sensors that respond to mechanical stimuli in the skin and internal organs. These breakthrough discoveries launched intense research activities leading to a rapid increase in our understanding of how our nervous system senses heat, cold, and mechanical stimuli.

Prior to the discoveries of David Julius and Ardem Patapoutian, the understanding of how the nervous system senses and interprets our environment still contained a fundamental unsolved question: how are temperature and mechanical stimuli converted into electrical impulses in the nervous system?

In the latter part of the 1990’s, David Julius saw the possibility for major advances by analyzing how the chemical compound capsaicin causes the burning sensation we feel when we come into contact with chili peppers. Capsaicin was already known to activate nerve cells causing pain sensations, but how this chemical actually exerted this function was an unsolved riddle.

After a laborious search, a single gene was identified that was able to make cells capsaicin sensitive. The gene for capsaicin sensing had been found! Further experiments revealed that the identified gene encoded a novel ion channel protein and this newly discovered capsaicin receptor was later named TRPV1. When Julius investigated the protein’s ability to respond to heat, he realized that he had discovered a heat-sensing receptor that is activated at temperatures perceived as painful.

While the mechanisms for temperature sensation were unfolding, it remained unclear how mechanical stimuli could be converted into our senses of touch and pressure. Researchers had previously found mechanical sensors in bacteria, but the mechanisms underlying touch in vertebrates remained unknown. Ardem Patapoutian, wished to identify the elusive receptors that are activated by mechanical stimuli.

The breakthrough by Patapoutian led to a series of papers from his and other groups, demonstrating that the Piezo2 ion channel is essential for the sense of touch. Moreover, Piezo2 was shown to play a key role in the critically important sensing of body position and motion, known as proprioception. In further work, Piezo1 and Piezo2 channels have been shown to regulate additional important physiological processes including blood pressure, respiration and urinary bladder control.