Breakthrough in opioid science could one day deliver better pain relief

A team of researchers at USF Health at the University of South Florida has uncovered a new way opioid receptors work, a discovery that could lead to the development of safer pain medications.

“Our overarching research aims to understand how opioids work so that we can ultimately provide safer options for chronic pain and develop therapies for opioid use disorders,” said Laura M. Bohn, Ph.D., senior associate dean for Basic and Translational Research and professor of Molecular Pharmacology and Physiology in the USF Health Morsani College of Medicine.

In recent papers published in Nature and Nature Communications, Bohn and her colleagues discuss their work studying opioid receptors and developing newer compounds that provide pain relief without leading to the side-effects that drive opioid-related overdose and deaths, such as breathing suppression.

Concerns over opioid use and misuse continue even as deaths from opioid overdose fall. Since the opioid epidemic was declared a public health emergency in 2017, it has claimed more than half a million lives. As of 2022, nearly 1 in 3 adults reported in a KFF survey that they or a family member had been addicted to opioids.

Opioids such as morphine, oxycodone and fentanyl provide pain relief by binding to mu-opioid receptors, which are specialized proteins in nerve cells. When opioids bind to these receptors in the brain, spinal cord or gut, they trigger a chain reaction that leads to blocking the transmission of pain signals to the brain.

Research by Bohn and her colleagues has focused on G protein–coupled receptors (GPCRs). They studied the effect of two agonists on mice and found that they increased and prolonged the pain-killing effects of morphine and fentanyl without the respiratory or cardiac effects.

“We’ve found that the first step of the chain reaction is reversible, and that some drugs can favor a reverse reaction over the forward reaction,” Bohn said in a news release. “We’ve studied two new chemicals that strongly favor the reverse cycle and, when administered at non-effective doses, can enhance morphine and fentanyl-induced pain relief while not enhancing the respiratory suppression effects.”

The two molecules studied, however, are viable drug candidates, and they have not been tested for toxicity or side effects. But Bohn said the research provides the framework for building new drugs. One compound developed by the research team is SR-17018. This compound activates the same pain-relieving receptor as morphine, oxycodone and fentanyl, and it does not produce respiratory suppression. Bohn said she believes that SR-17018 can be improved upon to make it a viable candidate.