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Researchers collaborating with National Institutes of Health to develop nonopioid drug for chronic pain

Ann Gregus and Matt Buczynski

Researchers from the School of Neuroscience Dr. Gregus and Dr. Buczynski, are teaming with the University of California San Diego and the U.S. National Institutes of Health (NIH) to develop a drug — now in its earliest stages — that can treat certain types of chronic pain without the addictive consequences of opioids.   

The drug compound, known as ML351, was discovered by researchers from the NIH, part of the U.S. Department of Health and Human Services. It is designed to inhibit the naturally produced enzyme 15-Lipoxygenase-1, which synthesizes bioactive lipids that contribute directly to chronic pain not relieved by common over-the-counter nonsteroidal anti-inflammatory drugs, such as ibuprofen. This lack of relief can lead patients to resort to more powerful drugs, including opioids, such as Oxycodone, and other narcotics.

“Our goal is to demonstrate the preclinical efficacy of ML351 for chronic pain that does not respond to nonsteroidal anti-inflammatory drugs and might otherwise be treated with opioids,” said Ann Gregus, a research scientist with the School of Neuroscience, who is working on the drug compound with Matt Buczynski, an assistant professor of neuroscience who specializes in drug addiction.

A paper published on the drug and its likely impact on treating certain types of chronic pain appears in this month’s issue of the medical journal PAIN. The paper was written by Gregus and Buczynski, with coauthors Tony Yaksh, a pain expert at the University of California San Diego, and Anton Simeonov, scientific director of NIH's and the National Center for Advancing Translational Sciences. Ganesha Rai, Dave Maloney, and Ajit Jadhav, all of the NIH, codeveloped the drug compound.

Acute pain that occurs from touching a hot stove helps protect us from severe self-injury, but chronic activation of these pain signaling pathways can be debilitating, Buczynski said. Presently, only a limited number of drugs exist for effectively treating chronic pain, such as that caused by autoimmune diseases. Current anti-inflammatory drugs, such as nonsteroidal anti-inflammatory drugs and steroids, help relieve pain by reducing inflammation, but for many types of chronic pain they are less effective.

ML351 targets a novel signaling pathway believed to be responsible for the development of chronic pain that does not respond to anti-inflammatory drugs. “ML351 may be effective for multiple types of pain, and our future studies will investigate its utility in other models of chronic pain,” said Gregus.

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