Medicine Nobel Prize Goes for Temperature and Touch Discoveries | Quanta Magazin...

Julius and his colleagues started with questions about receptors for heat and pain. To find answers, they turned to capsaicin, the compound that causes us to experience a burning and sometimes painful sensation when we eat chili peppers or other spicy food. Based on our physiological response to the chemical, which includes sweating, capsaicin seemed to be inducing the nervous system to register a change in body temperature. To figure out how, Julius and his team screened millions of DNA fragments for a gene that could induce a response to the compound in cells that typically don’t react to it at all. After an arduous search, and what the Nobel Prize committee called “a high-risk project,” the researchers identified a gene that allowed cells to sense capsaicin. It encoded a novel ion channel protein, later called TRPV1, that Julius and his team discovered could be activated by hot temperatures perceived as painful.

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Their discovery opened the door to the identification of several other receptors that are sensitive to temperatures both hot and cold. TRPM8, for example, is a receptor in the skin that responds to low temperatures; it was discovered through experiments that used menthol as a stimulus. (Julius and Patapoutian’s laboratories discovered TRPM8 independently in 2002.)

Quanta Magazine has previously covered in more detail the work on the somatosensation of heat and cold for which Julius and Patapoutian are being honored today.

But somatosensation is not just about the perception of temperature; it is also involved in the perception of touch and mechanical pressure. And while temperature could be transduced by ion channel receptors that tracked physiological changes in cells, touch seemed to demand a sensor that would react to mechanical stimuli. Mechanical sensors had been identified in bacteria but, two decades ago, had never been seen in vertebrates.

A 3D model of Piezo1, the first mechanical touch receptor to be discovered.

David S. Goodsell

That’s where Patapoutian and his colleagues came in. After pinpointing cells that responded to changes in pressure, they identified 72 potential genes that might encode an ion channel receptor to facilitate that sensitivity. Of those genes, they found just one — the last candidate they tested — that did so. It coded for a novel ion channel protein, Piezo1, that could be activated by mechanical force.

Patapoutian and his team demonstrated that Piezo2, another receptor from that protein family, played a critical role in perceiving touch and in sensing body movements. Since then, further research has shown that both Piezo1 and Piezo2 are needed for the regulation of various other internal processes, including respiration and blood pressure.

Scientists are continuing to build on Julius’ and Patapoutian’s work, not only to unravel how we sense our environment — both external and internal — but also in hopes of developing drugs and treatments for various conditions, including chronic pain.

What is somatosensation?

We often talk about having five senses: sight, hearing, smell, taste and touch. But as a category of sensation, touch is so broad that it really should be treated as more than one. Tactile perception is just one component of the body and brain’s somatosensory system, which also includes the perception of temperature, pain, body position and self-movement.

Samuel Velasco/Quanta Magazine

The ability to feel hot and cold, to recognize an object by touch alone, to respond to pain, to balance on a beam — all fall under the umbrella of somatosensation. The somatosensory system also helps to regulate many key internal physiological processes, including blood pressure, respiration, urination and bone remodeling.

How is somatosensation different from the other senses?

Receptors for the other senses are for the most part found in specialized sense organs — the retinas of the eyes for sight, the cochlea of the ears for hearing, the nose for smell, the tongue for taste. Somatosensory receptors, however, are found throughout the body: in skin, muscles, internal organs, bones, joints and other systems.

What makes the somatosensory system even more complex is that it needs to discriminate between sensations that are graded in intensity but sometimes sharply distinguished in their effect: Gentle warmth can build into searing heat, and what starts as a welcome embrace can become crushing pressure. Moreover, those thresholds can change depending on context: A light touch can feel uncomfortable or painful if one has a sunburn, and our experience of the same stimulus can similarly shift in different social settings. The somatosensory system has to integrate a wide range of different signals to correctly interpret what’s going on and how to respond.

How do somatosensory receptors work?

As Julius’ and Patapoutian’s work has shown, somatosensory receptors are ion channels. When stimulated — by some degree of temperature or physical force, or by a chemical compound — the channels open and allow charged particles to flow into a nerve cell, which in turn allows the cell to pass along somatosensory information in the form of electrical signals.

Even within one category of somatosensation, different receptors respond to different sets of stimuli. There are distinct receptors for specific ranges of temperature; receptors for sharp pain versus a dull ache; for a gentle touch or a rapid vibration or a firm pressure. Still others are tuned to how muscles or tendons might be contracting or stretching.

How do somatosensory impressions affect other processes in the body?

The different streams of information from somatosensory receptors are relayed along peripheral nerves, through the spinal cord and brainstem, into the thalamus, and ultimately into the somatosensory cortex, where they are integrated into the complex perceptions we experience.

While somatosensory signals are involved in the regulation of various internal physiological processes, they also feed back to the brain to affect perception and cognition. Researchers have found, for instance, that information about heartbeat doesn’t just help the brain regulate blood pressure levels; it also affects how the brain processes external and emotional stimuli, including fear, and therefore how we perceive and respond to the world around us. The same is true of signals coming from the lungs, gut and other organs: They exert a crucial influence in both directions. Some researchers are now exploring how somatosensory signals might even underlie a sense of conscious selfhood.

What about pain?

While the various types of somatosensory information are all vital for day-to-day activity and survival, their involvement in pain stands out in importance. It’s the job of pain to attract immediate attention and alert us to potential dangers, both external and internal. Free nerve endings respond to chemicals released by inflamed or damaged tissue, or to extreme levels of mechanical force that we perceive as painful. Different receptors distinguish between kinds of pain: sharp or pinching, dull or aching.

When somatosensory information isn’t processed normally, however, it can lead to oversensitivity to certain stimuli, and even to chronic pain. Researchers hope to develop therapies and treatments for such conditions by targeting receptors such as those that Julius and Patapoutian identified.

Editor’s note: David Julius receives research funding from the Simons Foundation, which also funds this editorially independent magazine. Simons Foundation funding decisions have no influence on our coverage.

This post has been updated with additional details about the award-winning work.

Klaus Hasselmann, Syukuro Manabe and Giorgio Parisi shared the Nobel Prize in Physics. Benjamin List and David MacMillan won the 2021 Nobel Prize in Chemistry.