Scientists search for opioid replacement

Researchers at the University of Texas Southwestern Medical Center argue a trio of antibiotics can be used to treat some kinds of chronic pain. If true, the combination could provide a safe, non-addictive alternative to the sort of opioids responsible for the U.S. addiction crisis. The multidisciplinary team of doctors and scientists published their report in the Proceedings of the National Academy of Sciences on Monday.

Nearly 30 years ago, study co-author and UT Southwestern neuroscientist Mark Henkemeyer discovered that neuropathic pain is linked to a particular protein receptor—EphB1—found on the surface of nerve cells. Scientists connect neuropathic pain to certain chronic suffering of cancer patients and diabetics. Henkemeyer also discovered mice genetically engineered with fewer EphB1 proteins experienced less pain, and those without the protein couldn’t feel neuropathic pain at all.

That gave internal medicine instructor and study co-author Mahmoud Ahmed an idea. Perhaps a molecule that could bind to the EphB1 protein would help prevent neuropathic pain. While looking through a database of Food and Drug Administration–approved drugs in a search for such a molecule, Ahmed came across a family of three tetracyclines. Doctors started using demeclocycline, chlortetracycline, and minocycline in the 1970s as antibiotics, and have safely prescribed them for decades.

The scientists tested the theory by combining the three drugs with EphB1 in a petri dish. As hoped, the molecules of the antibiotics bound to the protein and rendered it inactive. Tests on three live mice corroborated the theory.

Scientists still need to test the cocktail to see if it will successfully block the EphB1 protein in humans. And doctors also prescribe opioids for other kinds of pain than neuropathic.

In October, Purdue Pharma, maker of popular pain reliever OxyContin, agreed to an $8 billion settlement for its role in the epidemic of opioid addiction. Opioids are highly effective, but also highly addictive, and overdoses have been blamed for 450,000 deaths in the United States between 1999 and 2018 according to the Centers for Disease Control and Prevention.

“Unless we find alternatives to opioids for chronic pain, we will continue to see a spiral in the opioid epidemic,” lead author and pain specialist Enas Kandil said. “This study shows what can happen if you bring together scientists and physicians with different experience from different backgrounds. We’re opening the window to something new.”