A soft brush, a hot surface and an itch may feel like very different signals, but in mice they share a molecular helper: a protein called CRELD1. Researchers led by Bailong Xiao at Tsinghua University in Beijing found that the protein helps sensory nerve cells send strong messages about touch, temperature, pain and itch.
The finding, published in Nature Neuroscience, points to a possible way to study treatments for pain or itch. It does not show that a treatment exists, or that the same effect has been confirmed in people. Still, it offers a clue to how the body carries several kinds of sensory information from the skin toward the nervous system.
The team set out to find genes that shape sensation. Using CRISPR, a tool for changing DNA, researchers disabled selected genes in newborn mice and tested the animals as they grew. After checking their method with genes already known to affect sensation, they screened 20 candidates. Creld1 stood out because changing it affected so many responses.
Mice with the gene disrupted withdrew their paws less often when researchers touched them with fine filaments or a soft brush. They reacted less to painful pressure and took longer to respond to hot and cold surfaces. The team also removed Creld1 specifically from sensory neurons grouped beside the spinal cord and saw similar effects. After injections of histamine, a chemical that can trigger itch, the mice barely scratched. They also scratched less after other itch-inducing substances.
The animals had normal body weight, movement and coordination in the tests, making a general movement problem an unlikely reason for their weaker reactions. The researchers then looked at how the signals were being handled. Sensory neurons without CRELD1 could still detect the tested stimuli, suggesting the protein is not itself a receptor for touch, heat or itch.
Instead, CRELD1 appears to help with the next step: turning detection into electrical messages. Nerve cells use sodium channels, which let charged sodium particles cross the cell membrane and help start those messages. The researchers found that CRELD1 binds to several sodium channels and boosts their activity. Without it, sodium currents weakened, neurons needed stronger stimulation to fire and they produced fewer electrical impulses. Raising CRELD1 levels had the opposite effect, strengthening sodium currents and making mice more responsive to touch, heat and cold.
That broad role could make the meeting point between CRELD1 and sodium channels a possible precision target for future drug research. But important questions remain. In cultured cells, the researchers tested two human versions of CRELD1: one increased the activity of a sodium channel, while the other did not. They do not yet know which versions are most common in human sensory neurons.
Before the discovery can guide a treatment, researchers will need to learn whether the mechanism works the same way in people—and whether it is possible to ease pain or itch without blunting the everyday sensations that warn us about danger. For now, the mouse study offers a map of one step in the journey from detecting a stimulus to feeling it.