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Women & Science: Pain, Itch, and Inflammation

February 24, 2022

Dr. Diana Bautista has dedicated her professional life to the science of literal human connection: our sense of touch.

A Howard Hughes Medical Investigator and professor of cell and developmental biology at University of California, Berkeley, Bautista runs a lab that conducts basic scientific research on touch, particularly itch, pain, and inflammatory diseases.

“Among the five senses, we really know the least about our sense of touch,” Bautista said. “This is surprising given how important touch is in our everyday lives.”

She points to pain as an example of why we need touch to stay healthy and safe. Acute pain, the feeling you get when you touch a hot frying pan, acts as a warning—it triggers a reflex to pull your hand back and prevent tissue damage. Likewise, inflammatory pain from a sunburn will prompt protective behaviors, like covering up before you go back outside, and learning behaviors, like proactively wearing sunscreen.

Chronic pain, however, serves no purpose. It’s like a siren that keeps ringing long after the fire has been put out. It’s a serious problem, afflicting more than 10 million Americans every year. “Which is why we’re working to understand the mechanisms underpinning touch and pain,” said Bautista. She and her colleagues are trying to determine why some people’s pain goes away when they recover from injury or disease, while other people suffer from chronic pain for the rest of their lives.

Bautista’s lab focuses primarily on the first step of feeling physical touch, which is called transduction. In this step, sensory neurons convert a physical stimulus, like the pressure of a handshake or the prick of a pin, into the electrical signals the nervous system uses to communicate. By identifying how these signals are triggered, Bautista hopes to identify new therapeutic targets for mediating pain.

“Our challenge is to discover new genes that underlie the persistence of chronic pain so we can develop new therapies that target pain at its source.” she said.

One gene her lab is researching is TRPM8, which is responsible for sensing cold and menthol. To verify this gene’s function, the scientists set up a mouse experiment. They created a small two-room chamber with an open doorway between the rooms. One room had a comfortably heated floor plate, and the other room had a very cold floorplate. When a regular mouse was put in the chamber, it avoided the cold side. However, when a mouse lacking the TRPM8 gene was placed inside, it traveled between the two chambers indiscriminately, demonstrating no sensitivity to the cold.

The discovery of this gene’s role in cold perception could help lead to treatment for patients suffering from cold allodynia (oversensitivity to cold), chemotherapy-induced neuropathy, and even certain types of migraines.

Another gene Bautista’s lab is studying is S1PR3. Rather than cold, this gene regulates sensitivity to mechanical pain. To test this, the researchers poked mice’s paws with a pin. Normal mice responded to this sensation 100% of the time, whereas mice lacking S1PR3 responded only 40% of the time. This finding is important because the gene is also expressed in human skin, as well as in a variety of other species.

Finally, Bautista’s lab is studying chronic itch, a condition that will affect one in ten people at some point in their lifetime. Like pain, acute itch is protective; it helps to ward off burrowing insects that might carry disease. However, chronic itch can be debilitating.

Historically, chronic itch has been associated with diseases of the integumentary (skin) and immune systems. However, Bautista’s lab has found that the nervous system interacts with the immune system in ways that can trigger inflammation from the skin all the way to the spinal cord. These interactions, which occur early in the sensation of itch, play a significant role in later chronic states of itch and can even go so far as to affect the onset of asthma.

“We’re really excited about this research,” said Bautista. “Very basic science can lead to the discovery of novel therapeutics.”