Neuronal imaging system shows sensory activity in real time, study finds

A new study by UT Health San Antonio and Stanford University scientists brings us closer to understanding how the body detects different sensations such as pain, itch and touch.

When a person feels pain or another external stimulation, primary sensory neurons translate the message into electrical impulses to tell the body how to respond. While scientists knew this happened, they did not fully understand how different sensations are distinguished – until now.

For the first time, scientists at The University of Texas Health Science Center at San Antonio (UT Health San Antonio) and Stanford have developed an in vivo imaging system that shows in real time how neurons activate to indicate different sensations. Their findings were published in the July 2025 issue of Nature Communications.

The work is a major advance in understanding how the nervous system processes sensations and opens new doors for developing treatments for pain and sensory disorders.

Primary sensory neurons are responsible for somatosensation – the process of turning stimuli such as touch, pressure, pain, itch and proprioception (the body’s awareness of itself in space) into signals for the brain. But despite decades of research, the mechanisms by which these neurons distinguish between types of sensation have remained a mystery.

“We know that when there is a stimulus, like an injury, we have an instant, simultaneous sensation of pain. But we don’t know how we sense that as pain, versus touch, so easily,” said study co-author and principal investigator Yu Shin Kim, Ph.D., associate professor in the Department of Oral and Maxillofacial Surgery at the School of Dentistry at UT Health San Antonio. “That basic mechanism has been a major question in our neuroscience field.”

The breakthrough came from a genetically encoded voltage sensor called ASAP4.4-Kv, developed by the team. This “positively tuned” sensor increases fluorescence when neurons depolarize, which allows researchers to see how neurons communicate in real time in mouse models. The imaging system uses a sensor that lights up when a neuron is active. By viewing this under a powerful microscope, scientists can see exactly which neurons are firing and how they respond to different sensations.

“For the first time, we can see the electrical signals from these neurons and how they correspond to different types of sensation,” Kim said.

The technique also confirmed a long-standing hypothesis that after inflammation or nerve injury, neighboring sensory neurons begin to communicate electrically.

“We proved and obtained the data that after inflammation or injury, these neurons communicate electrically. They can signal extremely quickly so that each neuron communicates its activity to another,” Kim said. “This was only a theory before, but we are the first to visualize and confirm it.”

This imaging technique has many advantages over traditional electrophysiological recordings, which are time-intensive and invasive. The new method allows researchers to observe sensory neuron subtypes and track their activity continuously.

Applications for this technology span studies of chronic pain, inflammation, itch, temporomandibular joint (TMJ) pain, migraine and other somatosensory conditions.

“Previously, there was no tool or technique for us to perform some of these studies, and now we have one,” Kim said.

A new study by UT Health San Antonio and Stanford University scientists brings us closer to understanding how the body detects different sensations such as pain, itch and touch.

When a person feels pain or another external stimulation, primary sensory neurons translate the message into electrical impulses to tell the body how to respond. While scientists knew this happened, they did not fully understand how different sensations are distinguished – until now.

For the first time, scientists at The University of Texas Health Science Center at San Antonio (UT Health San Antonio) and Stanford have developed an in vivo imaging system that shows in real time how neurons activate to indicate different sensations. Their findings were published in the July 2025 issue of Nature Communications.

The work is a major advance in understanding how the nervous system processes sensations and opens new doors for developing treatments for pain and sensory disorders.

Primary sensory neurons are responsible for somatosensation – the process of turning stimuli such as touch, pressure, pain, itch and proprioception (the body’s awareness of itself in space) into signals for the brain. But despite decades of research, the mechanisms by which these neurons distinguish between types of sensation have remained a mystery.

“We know that when there is a stimulus, like an injury, we have an instant, simultaneous sensation of pain. But we don’t know how we sense that as pain, versus touch, so easily,” said study co-author and principal investigator Yu Shin Kim, Ph.D., associate professor in the Department of Oral and Maxillofacial Surgery at the School of Dentistry at UT Health San Antonio. “That basic mechanism has been a major question in our neuroscience field.”

The breakthrough came from a genetically encoded voltage sensor called ASAP4.4-Kv, developed by the team. This “positively tuned” sensor increases fluorescence when neurons depolarize, which allows researchers to see how neurons communicate in real time in mouse models. The imaging system uses a sensor that lights up when a neuron is active. By viewing this under a powerful microscope, scientists can see exactly which neurons are firing and how they respond to different sensations.

“For the first time, we can see the electrical signals from these neurons and how they correspond to different types of sensation,” Kim said.

The technique also confirmed a long-standing hypothesis that after inflammation or nerve injury, neighboring sensory neurons begin to communicate electrically.

“We proved and obtained the data that after inflammation or injury, these neurons communicate electrically. They can signal extremely quickly so that each neuron communicates its activity to another,” Kim said. “This was only a theory before, but we are the first to visualize and confirm it.”

This imaging technique has many advantages over traditional electrophysiological recordings, which are time-intensive and invasive. The new method allows researchers to observe sensory neuron subtypes and track their activity continuously.

Applications for this technology span studies of chronic pain, inflammation, itch, temporomandibular joint (TMJ) pain, migraine and other somatosensory conditions.

“Previously, there was no tool or technique for us to perform some of these studies, and now we have one,” Kim said.