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A Key Piece of the Pain Puzzle Is Solved

A way to treat neuropathic pain would block the stress signal causing it, instead of diminishing the nerve response.

By Heather Stringer|Monday, November 30, 2015
pain-puzzle
pain-puzzle
Diane Diederich/iStock

Most of us probably take for granted that physical pain — whether it be from a sports injury, a kidney stone or appendicitis — can be attributed to some form of inflammation and that it will end. Neuropathic pain, however, affords its sufferers no such luxuries. It’s chronic and unrelenting, and its cause is unknown, making treatment difficult.

It turns out that neuropathic pain is triggered when the body experiences endoplasmic reticulum (ER) stress, a condition in which the production and transport of protein exceeds the cells’ capacities, say researchers from the University of California, Davis. Because diabetics are at high risk of having neuropathic pain, the team studied diabetic rats that had neuropathic symptoms: hypersensitivity to touch and lack of heat sensation. And the rats’ nerve cells showed clear signs of ER stress.

When the researchers treated the rats with a compound that blocks ER stress, the pain symptoms disappeared. Conversely, healthy rats developed neuropathy when they received chemicals that induce the stress response.

“Medications have historically focused on turning down the nerve response to pain, but now we’ve found one way to block the stress signal that generates the pain,” says Bruce Hammock, corresponding author of the study, which was published in July.

While it usually takes years for a discovery to translate to new medication, there may be a shortcut in this case. A medication that blocks ER stress is already on the market to treat an entirely different condition called urea cycle disorder. It would take a horse pill of the current medication to quell neuropathic pain, Hammock says, but the compound has promise.

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