Pathway to safer opioids uncovered by research

Researchers may have uncovered new answers on how to create safer opioids, according to a major new study.

The research, first published in Nature, suggests the design of a new opioid to bypass the part of brain that feels pleasure, but still retaining the analgesic properties which make opioids one of the most effective pain relievers.

In a study, researchers looked at how opioids may have become so widely abused.

“We identified a major source of how mu-opioids mediate reward,” said lead author Daniel Castro, acting instructor in anaesthesiology and pain medicine at UW Medicine and part of The Bruchas Lab, which examines how neural circuits affect motivated behaviours. “We provided a blueprint of how the system works.”

They studied a part of the brain called the nucleus accumbens, a key region in the reward circuit of the brain. When we do anything that is considered rewarding, dopamine neurons project to this area of the brain and make us feel good and want more.

“Mu-Opioids, like morphine act on specific receptors in the brain, like keys in a lock,” said Michael Bruchas, UW professor of anaesthesiology and pain medicine. “We isolated a new brain pathway where these receptors exert powerful effects to promote reward consumption behaviour.”

They found that opioid receptors are in a part of the brain called the dorsal raphe nucleus located towards the back of the brain by the brain stem. They act to alter the communication between the raphe and nucleus accumbens, which are in the front of the brain. “This finding was pretty unexpected,” said Castro.

Bruchas said prior work had focused solely on how mu-opioid receptors alter dopamine transmission.

To create a safe opioid, pharmaceutical companies would need to either bypass or create ways to bias the drug’s effect away from the dorsal raphe to nucleus accumbens pathway, Castro said.

The study potentially opens many new avenues for more discovery on what other behaviours the system mediates or moderates, providing potentially new avenues for opioids or other drugs, which relieve pain.

According to the US Centers for Disease Control, overdose deaths involving opioids, including prescription opioids, heroin, and synthetic opioids (like fentanyl), have increased over six times since 1999. Overdoses involving opioids killed nearly 50,000 people in 2019, and nearly 73% of those deaths involved synthetic opioids.

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