When a house catches on fire, a smoke alarm inside can warn the occupants of danger. But imagine if the device could transform into something that could fight the fire as well.

In a new study led by Johns Hopkins researchers and published in Science, a multi-institutional team has shown in mice that the body’s “pain alarms” — sensory neurons — actually have such a dual function. In the event of a bone fracture, these nerves not only report the trauma but they also morph into “reconstruction commanders” that actively direct the cellular workforce to rebuild the skeleton.

“For the first time, we have mapped the circuitry of this neural network, defined which specific sensory neurons supply nerves to bone, determined how these neurons change after an injury and identified which signals they produce that are necessary to promote bone formation and repair,” says Zhao Li, a senior research specialist in the lab of pathologist Aaron James, and co-first author of the study.

To map the neural network, Li and his colleagues used a laboratory-engineered adeno-associated virus with peripheral nerve tropism (a strong attraction toward peripheral nerves that innervate bone) to label which dorsal root ganglion (DRG) neurons actually do the job. DRG neurons are nerves along the spinal cord that are critical in transmitting signals from peripheral nerves to the central nervous system.

“The technique, known as retrograde tracing, is akin to following a single electrical wire from a light bulb back through the walls to find where the circuit breaker lies,” says James.

“We combined retrograde tracing with a second technique, single-cell RNA sequencing isolation, to study individual innervating DRG nerve cells in mice — before and after bone fractures — and then isolated them to determine the proteins each one produces,” says James. “Putting the data for all of the profiled cells together, we created the first comprehensive single-cell atlas of bone-innervating sensory neurons, a map of the neural network and signals necessary for bone repair.”

The study’s findings, James says, provide “a potential target for drugs that might one day enhance bone healing, especially in people dealing with compromising situations, such as aging, diabetes or neuropathy.”