Scientists Reverse Chronic Pain in Mice Without Opioids

For millions living with chronic pain that won't quit, science just delivered something remarkable: a way to switch it off without opioids.

Researchers at Virginia Tech have reversed chronic pain in mice by blocking a specific enzyme pathway that amplifies pain signals in the nervous system. The breakthrough, published in the journal Pain, worked even after the pain had already become established, mimicking what actual patients experience.

More than 50 million Americans live with chronic pain, and 75 percent of them, mostly women, find little relief from existing medications. Many suffer from conditions like fibromyalgia and chronic back pain that leave no visible damage to treat, making them especially difficult to manage.

Neuroscientist Ann Gregus and her team focused on nociplastic pain, a category that includes conditions where the nervous system itself has changed how it processes signals. Unlike broken bones or inflamed joints, this type of pain persists without any apparent injury, often leading doctors to dismiss patients' suffering.

The research team discovered they could erase pain behaviors in mice by shutting down enzymes that produce molecules known to intensify pain. When they gave mice these compounds, tactile sensitivity vanished and grip strength returned to normal.

The finding came partly by accident. When pandemic shortages forced the team to work with different mouse strains, they stumbled onto one that developed persistent pain behaviors remarkably similar to human chronic pain conditions.

Why This Inspires

One of the compounds tested is already in Phase II clinical trials for another disease, meaning it has proven safe in humans. That could fast-track its path to testing for chronic pain, potentially shaving years off the typical development timeline.

Gregus herself lives with migraines and nerve pain, giving her personal insight into how current treatments fail patients. "I know what it's like to live with pain every day and be told there's nothing else that can be done," she said.

The approach targets a completely different biological pathway than standard anti-inflammatory drugs, explaining why it works when other medications don't. It also avoids the addiction risks that make opioids dangerous for long-term use.

The team is now testing whether the same strategy works for chemotherapy-induced nerve damage and diabetic neuropathy, conditions that affect millions worldwide. If successful, it could represent the first new class of non-opioid chronic pain treatment in years.

For people told their pain is "all in their heads," this research offers validation: there's a clear biological mechanism at work, and now there's a way to target it.