For a person with nerve damage, even the softest touch can trigger pain. This increase in touch sensitivity, known as tactile allodynia, relies on the activity of a protein called STOML3.
Now, researchers led by Gary Lewin, Max Delbrück Center for Molecular Medicine, Berlin, Germany, show that inhibiting STOML3 with a newly identified molecule can take the pain out of touch, at least in mice.
Lewin and his colleagues searched for molecules that could disrupt how STOML3 functions in nerve endings that sense touch. Of the thousands they trawled through, only two fit the bill, dubbed OB-1 and OB-2.
When injected directly into the paws of normal mice, OB-1 caused a large fraction of nerve fibers that sense touch to fall silent. Moreover, OB-1 reversed the heightened sensitivity to touch seen in mice with experimental nerve damage.
Miriam Goodman, Stanford University, US, who was not involved in the study, says that OB-1 and OB-2 could help extend research on normal, and painful, touch sensation.
“These molecules seem to be effective in interrupting touch hypersensitivity,” she adds, “and that is something we really don’t have any other tools for.”
The study was published online December 12 in the journal Nature Neuroscience.
When touch hurts
Allodynia is a common symptom of nerve damage. Yet drugs routinely used to treat allodynia, such as gabapentin, only work for a small proportion of patients, says Lewin. Worse, they often cause a slew of side effects.
“Gabapentin was originally developed as an anticonvulsant [anti-seizure] medication, not as a pain drug,” Lewin explains.
In 2007, Lewin and colleagues found evidence that STOML3 might serve as a good target for painkillers. In contrast to normal mice, those genetically engineered to lack STOML3 did not become overly sensitive to touch after their nerves were experimentally injured. This suggested that STOML3 somehow contributed to allodynia.
“At that point, there was the idea of, ‘How can we capitalize on that?’” says Kate Poole, University of New South Wales, Sydney, Australia, one of the lead authors of the new study.
An answer did not come until years later when Poole and Lewin learned the basics of how STOML3 works. Specifically, they discovered that the protein, which sits in the cell membrane of neurons, makes touch more sensitive by forming clusters.
That knowledge spurred the search for molecules that could prevent STOML3 from clustering in the cell membrane—something that OB-1 was able to do. The researchers also found that, after injecting OB-1 directly into the paws of normal mice, many nerves did not respond to pokes of the skin.
The researchers then tested whether they could counteract painful touch in mice that had different types of experimental nerve damage. Depending on how their nerves were damaged, the animals recovered their normal sensitivity to touch shortly after receiving OB-1.
Still, “there’s not enough information about the properties of [OB-1 and OB-2] to know if they would make good drugs” for people, says Goodman. For example, OB-1 was injected into the animal’s paw, rather than delivered throughout the body, so it’s unclear if the compound would have risky side effects.
Lewin might have a better idea of that soon enough. He’s now collaborating with researchers who specialize in developing drugs.
“Eventually, what we’d like to do is find something we could go into clinical trials with and find out whether it works in humans,” says Lewin. –Matthew Soleiman
Matthew Soleiman is a science writer currently residing in Nashville, Tennessee. Follow him on Twitter @MatthewSoleiman