UC Irvine researchers patent formula to block the transition from acute to chronic pain

Anyone who has experienced chronic pain knows how debilitating it can be. Just ask Daniele Piomelli, PhD, who has dealt with pain twice in his life: once after a minor surgery, and again with a bad bout of back pain that lasted for four months.

“I don’t wish chronic pain on my worst enemy,” says Piomelli, a Distinguished Professor of anatomy and neurobiology in the UC Irvine School of Medicine. His post-surgery experience in the late ’90s is what first prompted his research into pain. In recent years, he has looked more specifically at how acute pain transitions to a state of pain chronicity.

“It’s a phenomenon that happens a lot more frequently than people appreciate,” says Pionelli. For example, roughly 30% of individuals who have a mastectomy, and up to 40% of those who have open-chest surgery, experience chronic pain. Up to 85% of people who require an amputation experience phantom limb pain.

“This is a problem I felt was understudied, so we decided to tackle it,” says Piomelli.

He led a study working with colleagues at UC Irvine, including postdocs Yannick Fotio and Alex Mabou Tagne, which revealed a specific molecular mechanism that controls the transition from acute to chronic pain. Through that work, the team noticed metabolic adaptations to the bioenergy demands imposed by an injury.

“To be able to cope with the enormous amount of neural activity that follows an injury, you need proteins and lipids, and you’re losing out on a bunch of nutrients as they’re being consumed,” explains Piomelli. “So we asked if this drop in nutrients was just an epiphenomenon — an innocent bystander, as we say? Or was it causative of the pain?”

The answer to that question appears in a paper recently published in Cell Reports, “Metabolic Reprogramming in the Spinal Cord Drives the Transition to Pain Chronicity.” Furthermore, the findings led Piomelli, Fotio and Tagne to file a patent application for “compositions for preventing transition from acute to chronic pain.”

“The lack of nutrients was causative,” confirms Piomelli. “We basically made a list of the deficient nutrients, and we added them together into a ‘medicated diet.’ Very much to our shock, that blocked the transition to pain chronicity.”

The modified diet was successful in four out of five mouse models, including three for post-surgical pain. “The only model in which it didn’t work was for inflammatory pain,” says Piomelli, who still can’t believe the results. “I’m a pharmacologist, my father was a pharmacist and my grandfather was a pharmacist, so I’ve always dealt with drugs. Seeing a food be so effective was truly mind-boggling.”

Through their startup Nectaris, the researchers hope to bring this mixture to clinic. “The big question, of course, is if this is also true in humans,” says Piomelli. “I hope we produce something useful for the public. I really believe that this would make life better for many people.”

In addition to the modified diet, Piomelli is also exploring ways to disable N-acylethanolamine acid amidase (NAAA) — an intracellular enzyme. “NAAA is the gatekeeper for pain chronification,” says Piomelli. “If we can inhibit this enzyme after surgery, that’s another way to prevent post-surgery chronic pain.”