Animal models and experimental medicine and the Nobel Prize in Physiology or Medicine 2021—TRPV and PIEZO receptors for temperature and touch sensation

1Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Beijing, China 2Comparative Medicine Center, Peking Union Medical College, Beijing, China 3NHC Key Laboratory of Human Disease Comparative Medicine, Beijing, China 4Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Beijing, China 5Chinese Association for Laboratory Animal Sciences, Beijing, China


| INTRODUC TI ON
The senses of temperature and touch are among the most basic physiological functions in animals and humans. Stimuli from the surrounding environment or physical objects interact with receptors, mainly temperature and tactile sensory receptors, and are converted into information, or neural signals. Subsequently, all the encoded neural signals are transmitted through afferent (or sensory) neural fibers to interneurons or the central nervous system, and thence through efferent neurons (or motor neurons) to effector organs, for example muscles. These steps form a complete reflex arc comprising the body's response to external stimuli. Perceptions of the external stimuli help our bodies to react, to make decisions and motor responses, so that we can feel, interpret and interact with our external and internal environment.  In the late 1990s, Dr Julius and colleagues tried to isolate a functional cDNA encoding a capsaicin receptor in sensory neurons. In 1997, they shared their discovery of a non-selective cation channel TRPV1 (transient receptor potential vanilloid type 1, or VR1 for short), which can also be activated by noxious temperature stimuli.

| ANIMAL MODEL S FOR RE S E ARCHING TEMPER ATURE-S ENS ING MECHANIS MS
Using laboratory rats for their experiments, they found that VR1 is This indicated that the TRPV1 receptor is essential to thermal hyperalgesia sensation. 11 Thereafter, another chemical, a cooling agent, menthol, was used to identify the receptor for cold sensation. In 2002, Patapoutian and colleagues described the characterization of TRPM8, which can be activated both by menthol and cold temperatures. 12,13 The ion channels TRPV1 and TRPM8 belong to the family of transient receptor potential (TRP) ion channels. Later, other related receptors for more delicate thermal sensation, the TRP family, were identified, 14 and these molecular receptors for temperature sensation were subsequently decoded.
Rodent models are useful for temperature research and have helped to provide a comprehensive understanding of temperature sensation. Using genetics and in vivo calcium imaging, researchers found that heat and cold could send major inputs to TRPV1 + or TRPM8 + DGR neurons and induce robust calcium responses in spinal neurons. 15 Research into the properties of TRP receptor families, including their physiological and pathological functions in thermal sensation, chronic inflammatory pain and cancer pain, continues to take place. [16][17][18][19][20][21][22]

| ANIMAL MODEL S FOR RE S E ARCHING TOUCH PERCEP TI ON
The basic question of touch and pressure sensation is similar to that of the molecular mechanisms of temperature sensation: how do the external signals convert into electrical neural signals?
Originally, Ardem Patapoutian and colleagues identified a mechanosensitive cell line, Neuro2A cell. By poking at the cells with a micropipette, they analyzed 72 candidate genes and finally identified an unknown mechanically activated cation channel, which was later named PIEZO1, named after the Greek word for pressure "piesi".

ACK N OWLED G M ENTS
We would like to thank Professor You Wan and Professor Ming Yi from Peking University for their outstanding research in the field of TRPV1 and pain. Their kind and careful guidance in both science and daily life points the way for my scientific research. We thank Dr.
Yuxiang Chen from Capital Medical University for excellent manuscript editing. We are grateful to Nobel Prize laureates, who have promoted the progress of science and mankind for over a century.

CO N FLI C T O F I NTE R E S T
The authors have declared no conflicts of interest.