[♪ INTRO] This episode was made in  partnership with the Kavli Prize.

The Kavli Prize honors scientists for  breakthroughs in astrophysics, nanoscience, and neuroscience – transforming  our understanding of the very big, the very small, and the very complex. And in 2020, the Kavli Prize in  Neuroscience was awarded to two scientists, David Julius of University of California,  San Francisco and Ardem Patapoutian of Scripps Research Institute, who studied  how we feel pain, from heat to pressure.

We did not fully understand how that basic  bodily function works until recently! They cracked the code of these sensations  with the help of lots of hot peppers and skin pinches. Pain can come from  quite a few different sources, but their research suggests that pain  from various sources can be processed by our bodies in  a surprisingly similar way.

Hot stoves and habañeros might seem  like very different kinds of heat, but they trigger the same internal response. You see, some of your body’s  pain sensors are sensitive to a chemical found in hot peppers called capsaicin. This chemical makes it easier for  molecules with a positive charge, or cations, to pass through the  outer layer of a pain receptor cell.

When cations like sodium and calcium pass  into a cell, its internal charge builds up enough current to activate the cell to do  its job. In this case, the cell’s job is to alert the rest of the body to  potentially dangerous stimuli like heat. But until now, we didn’t know how capsaicin  triggers this response in pain cells.

So David Julius’s team of scientists went  on a search to find the gene that makes capsaicin-responsive cells. Once they  found that gene, they confirmed that it was only found in sensory  neurons that respond to heat. So next, they tested how these cells  respond to different kinds of heat.

In one experiment, they put some tissue  into a petri dish and added a 65-degree celsius solution for it to float around  in. And in another experiment, they added capsaicin to the solution that the tissue  was floating in. Both kinds of heat produced the same physiological response  and activated cells in their dish.

And they found that the mechanism was  calcium-dependent. Within seconds of applying heat, they measured more calcium  in the pain cells. So both kinds of heat triggered similar increases  in current flowing into the pain cells, which were not  observed in control cells.

From these experiments, they discovered that capsaicin opens a channel that lets  calcium flow in and activate pain cells. And while several different  kinds of heat can trigger this mechanism in similar ways, heat is  not the only thing that triggers it. Ardem Patapoutian’s research  team figured out that these cation channels can also be activated by pressure.

Because pain doesn’t just come  from touching a hot stove. It can also come from like  closing a drawer on your fingers. In an experiment where the researchers  applied pressure to individual cells, they found that greater pressure leads  to more current flowing into the cell.

So it works in a similar way to heat sensation. And they named the gene that makes  pressure-sensitive ion channels Piezo after the Greek word “piesi,”  which means “pressure.” And then they found similar Piezo genes  all over the plant and animal kingdoms. Vertebrates, like us, have two piezo genes.

The channel that Piezo1 encodes for  conducts cations with a preference for calcium, similar to what was  described by Julius’s group. And it’s found around the membrane, where  this kind of channel would be useful. Piezo2 is similar to Piezo,1 but it works faster.

The Patapoutian lab concluded that  without functioning Piezo2 channels, you wouldn’t be able to differentiate  between painful and harmless touch. Everything would just feel like a nice touch. They were able to do this in mice, with  Piezo2 channels that they could basically turn on and off, and when they  turned the Piezo2 channels back on, they would recover their ability  to sense painful stimuli.

Now, you might be thinking you’d like  to permanently close all your Piezo channels because pain isn’t great. But  individuals with CIPA, or congenital insensitivity to pain and anhydrosis,  don’t respond to noxious stimuli. They often inadvertently harm themselves  and many die before the age of 25.

So pain is protective and incredibly  important to us. But we need a balance. On the other end of the spectrum, there  are people who are oversensitive to touch and experience allodynia.

If you have  allodynia, you might feel chronic pain triggered by a harmless  touch, from like a paintbrush. And Patapoutian’s team believes that Piezo2 is an excellent candidate to treat allodynia. These studies are piecing together the  pain puzzle so more people can live in that balanced sweet spot.

And the more  we understand the science behind the everyday sensations of heat, and  cold, and pressure, the better we can understand how to treat  conditions related to them.   Thanks for watching this episode of SciShow! And thank you again to The  Kavli Prize Foundation for supporting this episode and  for supporting science.   The Kavli Prize in Neuroscience is  awarded for outstanding achievement in advancing our knowledge and understanding  of the brain and nervous system.   They also award a nanoscience and  astrophysics prize, honoring researchers for transforming our understanding of  the science of the atomic, molecular, and cellular structures, and  advancing our knowledge of the origin, evolution, and  properties of the universe.   If you want to learn more about  2020’s Neuroscience laureates, David Julius and Ardem Patapoutian,  you can visit their page on the Kavli Prize website by clicking  on the link in the description. [♪ OUTRO]