Stopping Chronic Pain Before it Starts

Irvine, Calif., Sept. 2, 2026 — Chronic pain is one of medicine’s most stubborn puzzles. A sprained back, a surgical incision or a pinched nerve heals – and yet, for millions of people, the pain never fully goes away. Why some injuries fade into memory while others evolve into a lifelong condition has remained largely a mystery.

A new study from researchers at the University of California, Irvine offers a striking possible answer, and it comes from an unexpected direction: the same amyloid biology long associated with Alzheimer’s disease. The study, which appears in Science Translational Medicine, suggests that chronic pain may be driven by a distinct biological process that begins shortly after injury. If the same pathway is confirmed in people, future treatments might aim to prevent pain from becoming long-lasting rather than only managing it after it’s established.

Led by Daniele Piomelli, Distinguished Professor of anatomy and neurobiology, the research team used mice to trace how an injury sets off a chain reaction in the spinal cord. Days after a hind paw injection designed to mimic tissue injury, a class of cells called oligodendrocytes, whose normal job is to maintain the fatty insulation around nerve fibers, began behaving strangely – cutting back on the machinery needed to produce that insulating material, called myelin.

That shift didn’t stay contained. Nearby nerve fibers began to lose structural integrity, and neurons responded by churning out amyloid precursor proteins that generate beta-amyloid 42. These sticky protein fragments are notorious for clumping into the plaques found in Alzheimer’s-affected brains. In the mice, elevated beta-amyloid appeared in the spinal cord precisely during the window when pain was shifting from a temporary nuisance to a lasting condition.

“We were not looking for a connection to amyloid biology; it emerged from following the data,” Piomelli said. “What surprised us most was how central this pathway turned out to be. It wasn’t just present alongside chronic pain. When we blocked it, the chronic pain simply didn’t develop.”

Read the full press release in UC Irvine News.