Scientists Discover How to Reverse Chronic Back Pain Without Opioids—And It's a Game-Changer

Researchers at Virginia Tech have discovered a breakthrough method to reverse chronic pain in laboratory models by targeting a specific enzyme system in the spinal cord, potentially offering the first new non-opioid treatment option in years for conditions like chronic low back pain. The study, published in PAIN, showed that blocking this single pathway erased established pain behaviors in female mice, marking a significant shift from simply preventing pain to actually reversing it.

What Makes This Discovery Different From Current Treatments?

Unlike traditional pain medications that mask symptoms, this approach targets the root biological mechanism behind nociplastic pain—a poorly understood category that includes chronic low back pain, fibromyalgia, and some migraines. Current treatments like nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids often fall short for these conditions, leaving more than 50 million Americans with inadequately managed chronic pain, with 75% of these patients being women.

"Earlier studies have focused largely on preventing development of pain—so the key finding here is the reversal of an established pain state and associated functional deficits, which more closely mimics the human experience," said Ann Gregus, assistant professor in Virginia Tech's School of Neuroscience. "It provides hope for people living with daily, persistent pain that does not respond to conventional treatments."

How Does the New Treatment Actually Work?

The research team discovered that chronic pain involves an immune receptor in the spinal cord that activates enzymes, which then release molecules that amplify pain signals. By using highly selective compounds developed at the National Institutes of Health, they were able to shut down this enzyme system completely. The results were remarkable in the mouse models: tactile and cold pain hypersensitivity vanished, and grip strength returned to normal levels.

The breakthrough came partly by accident during the pandemic when supply shortages forced researchers to use a different strain of female mice. These mice developed persistent pain behaviors, cold sensitivities, and grip force deficits typical of arthritis conditions, providing a better model for human chronic pain experiences. "It was serendipity," Gregus said. "We were working with whatever limited resources were accessible, and we ended up with a model that gave us clues about how pain transitions from acute to becoming chronic that we may not have discovered otherwise."

What's Next for This Research?

The researchers plan to test whether the same enzyme-blocking strategy works in models that mirror more complex human diseases. Their next steps include investigating:

• Chemotherapy-Induced Peripheral Neuropathy: Pain that can linger for years after cancer treatment, affecting quality of life for survivors
• Diabetic Neuropathy: A leading cause of disability worldwide that affects millions with diabetes
• Other Chronic Pain Conditions: Testing the approach across different types of persistent pain that don't respond to current treatments

One of the compounds tested is already in Phase II clinical trials for another disease by Veralox Therapeutics, which could significantly shorten the path to human trials for chronic pain treatment since it already has human safety data. "If we can reverse chronic pain in those settings without the abuse liability of opioids," Gregus said, "that's when we know we're ready to think about clinical trials."

"Chronic pain patients are often told pain is all in their heads and they just have to learn how to tolerate it," Gregus explained. "But what we're showing is that there is a clear biological mechanism—and one we can target." For Gregus, who lives with migraines and peripheral neuropathy herself, this research represents more than scientific advancement—it's personal motivation to find solutions for people who have exhausted conventional treatment options.

The study's success across multiple pain models and species makes it particularly promising for future human application. "It's rare to see a drug work in reversing so many different pain models in multiple species," Gregus noted. "That makes it especially exciting to think about what it could do for patients." If clinical trials prove successful, this could represent the first truly new class of chronic pain treatment in decades, offering hope for reversing rather than just managing persistent back pain and related conditions.