CHICAGO — Taking opioids for years does not seem to improve pain and functioning in people with chronic back pain, according to a new Northwestern University study that compared 70 long-term opioid users to 70 similar patients not taking opioids.
The study also found large differences in brain activity between the two groups and identified new molecular markers, including some involving serotonin receptors, that could lead to new treatment for pain and for tapering off opioids.
Based on these findings, the Northwestern scientists plan to test whether an antidepressant, which targets the same serotonin molecular pathway identified in the study, can help treat chronic pain and opioid dependence.
The study, published on Oct. 1 in the journal Brain , comes with an important nuance. Even though the opioid group didn’t fare better, it also wasn’t much worse off.
“The psychological and brain properties of the participants on long-term prescription opiates were essentially intact,” said senior study author A. Vania Apkarian , director of the Center for Translational Pain Research at Northwestern University Feinberg School of Medicine.
“That’s good news because there’s this fear nowadays that as soon as you start ingesting opiates, your brain is going to go crazy, and it doesn’t,” Apkarian said. “But the bad news is that we saw no sign that their pain had gotten any better by using this drug for so many years.”
Roughly 5 million U.S. adults use prescription opioids regularly to manage chronic pain. Apkarian said it’s important to note that the study participants were taking low or moderate doses under medical supervision. He also said that this was the first study to look at long-term opioid consumption and brain properties.
Findings
The patients in the opioid group had been taking daily prescription opioids for an average of 7.8 years for chronic back pain. The other group included tightly matched patients with chronic back pain, but not taking opioids.
The two groups reported nearly identical levels of pain, about 5.4 on a 10-point scale. The opioid group, however, had slightly worse results on physical function and mental health.
Besides comparing participants’ pain, function and emotional health, the scientists also examined their brains using functional MRI, which measures brain activity by tracking changes in blood flow. Reassuringly, the team found little evidence that years of taking opioids altered the brain’s anatomy.
But in terms of spontaneous brain activity, or how brain regions function and communicate, the difference between the two groups was striking. And that was particularly true in the mesocorticolimbic network, a system involved in reward and motivation, and in the prefrontal cortex, a region that supports decision-making.
An ‘exciting’ tech to see the brain
To better understand those differences, Apkarian and colleagues built a new computational technique that combined the MRI data of the participants with published brain maps of neurotransmitter receptors.
With their novel method, the scientists identified molecular signatures associated with different aspects of chronic pain as well as with long-term opioid use. Those distinct signatures involved activity in serotonin and opioid brain receptors.
“For me, that’s the most exciting part of the study,” Apkarian said. “We identified molecular markers of different states of that brain in chronic pain patients. And this gives us clues for what kind of new treatments to pursue, what kind of drugs to try and what kind of drugs not to use.”
For the study, Apkarian’s team also looked at 21 patients who completed a four-week pain rehab program. Eight of the patients managed to reduce opioid use by more than 30%. And their brain activity showed changes linked to the serotonin and opioid receptors, adding evidence that these molecular markers may help guide new treatment for both chronic pain and opioid tapering.
Other Northwestern study contributors include first author Marwan Baliki and co-authors Andrew Vigotsky, Gaelle Rached, Rami Jabakhanji , Lejian Huang , Paulo Branco, Joana Barroso , Olivia Cong, Maria Centeno, Sam Cermak, James Griffith and Thomas Schnitzer .
The study is titled, “Multi-molecular adaptations of long-term opioid use in chronic pain.” It was supported by the National Institutes of Health (grant P50DA04412) and the U.S. Department of Defense (grant W81XWH-17-1-0426).
Brain
Multi-molecular adaptations of long-term opioid use in chronic pain
1-Oct-2026