LAUSR

Three apparently unrelated findings led to the discovery of the temperature receptors: a better understanding of pain-sensing, the molecular nature of the channels in charge of touch and proprioception, and the 2021 Nobel Prize in Physiology or Medicine bestowed to David Julius and Ardem Patapoutian. In 1953, state-of-the-art research in temperature sensing concluded that temperature afferent fibers came in two flavors, “cold” and “warm,” characterized by discharging by a lowering in temperature and an increase in temperature, respectively (1). Hensel and Zotterman had previously described the sensitizing effect of menthol upon cold receptors (2). It is also an old observation that acute application of capsaicin, the active component of chili peppers, causes intense pain, and that its repeated administration renders animals insensitive to the action of this vanilloid compound (3). The fact that capsaicin induces a depolarization of ventral root neurons from the isolated rat spinal cord suggested to Theriault et al. (4) that capsaicin’s acute and chronic effects on nociception could be explained by a direct action on primary sensory neurons. On the other hand, McCarter et al. (5) demonstrated the existence of mechanosensitive currents in rat dorsal root ganglion (DRG) cells, clearly pointing to the existence of mechanosensitive ion channels as being responsible for the sense of touch. Since temperature is an “intensive” thermodynamic parameter (i.e., one that does not depend on the size of the system), it was difficult to think of specialized temperature receptors. However, the seminal 1997 Nature paper from Julius’ laboratory demonstrated that living beings have evolved to transduce all stimuli coming from the external world using ion channels, including temperature (6). Caterina et al. (6) used an expression cloning strategy to search for the capsaicin receptor and found a single clone in which capsaicin induced a significant increase in cytoplasmic calcium. The isolated cDNA coded for a channelforming protein, now known as TRPV1, belonging to the transient receptor potential (TRP) family and expressed in smallto medium-diameter neurons of