It is hard to believe that a drug effective at relieving acute pain would not trigger a reward response. After all, it’s the reward response to drugs that results in people using them, not as pain relievers, but out of habit and from fear of withdrawal.

The holy grail of pain relief is something like ibuprofen that relieves pain but is “completely non-addictive.” For severe pain, there’s no substitute for opioids such as morphine, oxycodone, hydrocodone, fentanyl, and codeine. Unlike ibuprofen, they are habit-forming, resulting in withdrawal symptoms once a dependency has been established.

Today, new research out of Duke University shows there is hope for using the pain-relieving properties of opioids without triggering dependency or addiction.

The research is led by Dr. Michael Raphael Tadross, an associate professor in neurosurgery at Duke University School of Medicine. Dr. Tadross’ career path is unique and includes a B.S. in electrical and computer engineering from Rutgers University, an M.D. and Ph.D. in biomedical engineering from Johns Hopkins University, and postdoctoral studies in neuroscience at Stanford University.

Dr. Tadross’s lab at Duke University “develops technologies to rapidly deliver drugs to genetically defined subsets of cells in the brain.” The paper published this month in the journal Nature documents his latest efforts at separating relief from reward:

Here we show that associative opioid-reward learning can be blocked even under conditions that elevate dopamine in the nucleus accumbens.

Dr. Tadross developed an analog of naloxone, the drug that is used to stop opioid overdoses in their tracks. Naloxone, or Narcan, has saved thousands of lives and been credited with bending the curve on overdose deaths.

In research with mice, Dr. Tadross and his team used their analog of naloxone to render cells in the nucleus accumbens “morphine-insensitive.” The mice showed no preference for morphine access. This was accomplished without reducing dopamine in the nucleus accumbens.

The result is the possibility to “preserve acute analgesia while limiting early associative reward learning.” The separation of relief from reward.

Dr. Tadross described the effects in an article in Technology Networks Drug Discovery: “You may still feel the pain, but you aren’t bothered by it.” By targeting a group of neurons, they were able to “prevent the drug-related associations that underlie reward learning.”

“What’s unique about our study is that it shows that dopamine elevation can be separated from learned drug preference,” Dr. Tadross said. The result could be drugs blended with opioids that retain their pain-relieving properties without triggering dependency. This is the kind of science we need right now.

Written by Steve O’Keefe. First published August 26, 2026.

Sources:

“A cholinergic hub in the nucleus accumbens gates opioid-reward learning,” Nature, August 5, 2026.

“Research Could Reduce Opioid Addiction Risk While Maintaining Pain Relief,” Technology Networks Drug Discovery, August 10, 2026.

“Targeting small group of brain cells may reduce opioid addiction risk,” NewsMedical Life Sciences, August 7, 2026.

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