About 20 percent of people with diabetes will eventually experience peripheral neuropathy – pain that is often described as burning, shooting, stabbing or tingling in the toes and fingertips.
According to a study published in the journal Nature Neuroscience, scientists have discovered how to reverse this pain. They have identified and successfully tested a molecule that can inhibit the function of a protein that turns touch receptors into pain receptors under the skin. They did their research in mice, which have a similar neural and cellular make up as humans.
The scientists are hopeful that a new drug can be developed to treat patients with diabetic neuropathy, as well as other nerve damage-related pain, but note that nerve damage itself generally can’t be repaired.
“Therefore, proper pain management can significantly improve the lives of people with diabetic neuropathy and others living with nerve damage,” said co-author, Dr. Kate Poole, who conducted the research at the Max Delbruck Centre for Molecular Medicine in Germany, and is now based at UNSW’s School of Medical Sciences.
Skin has specialized receptors that allow the perception of the slightest touch and can even detect extremely small movements. These movements are transformed into electrical signals via channels at sensory endings in the skin. The sensitivity of these channels is controlled by a protein called STOML3, which is required for normal receptor function.
This protein as a target for blocking pain receptors found underneath the skin. During their reserarch, the scientists identified a single molecule after searching through a catalogue of 35,000 compounds. When this molecule was tested on the sensory endings in the skin of mice, they found STOML3 clustering was inhibited and pain receptors were silenced.
Inhibiting STOML3 did not significantly affect the non-pain-related touch sensitivity of the mice, ensuring touch sensitivity was not sacrificed at the expense of turning off pain receptors.
“While a potential new treatment for the pain associated with diabetic neuropathy is still some years away, the research is an important first step in changing the accepted thinking around how to treat the condition,” Dr. Poole said.
“Directly targeting nerve receptors in the skin could help manage pain in a way that does not trigger the negative side effects of drugs that act on the body’s central nervous system, which is how most current treatments work.”
“If human patients respond the same way, this will represent a major step in treating a neuropathology that has a devastating effect on the lives of many people,” Professor Gary Lewin, from the Max Delbruck Centre for Molecular Medicine.
“We will be studying force sensing molecules in the cells that make our cartilage to see if we can identify a way to reverse the cartilage damage that occurs when people develop osteoarthritis,” Dr. Poole said.
“This also involves going back to the drawing board to look more closely at force sensing proteins in other cells and tissues so we can increase our understanding of how human cells sense their physical surroundings.”