Long-term opioid use for chronic back pain does not improve patient pain levels or physical function compared to patients not taking the medication, according to a study published Oct. 1 in the journal Brain.
Opioid Users Report Similar Pain Levels to Non-Users
The study, led by the Northwestern University Feinberg School of Medicine, tracked 70 patients who had been taking daily prescription opioids for chronic back pain for an average of 7.8 years. Researchers compared these individuals against a control group of 70 patients who suffered from chronic back pain but did not use opioids. Both groups reported nearly identical pain levels, averaging 5.4 on a 10-point scale.
While the pain scores remained the same, the opioid-using group showed slightly lower results regarding physical function and mental health. Senior study author A. Vania Apkarian, director of the Center for Translational Pain Research, noted that the participants were taking low or moderate doses under medical supervision. "The psychological and brain properties of the participants on long-term prescription opiates were essentially intact," Apkarian said. That is encouraging since contemporary worries suggest starting opiates instantly deranges your brain, whereas it actually avoids doing so. On the flip side, however, we observed zero evidence that taking this medication over multiple years provided any pain relief.
Identifying Brain Activity Differences
Researchers used functional MRI (fMRI) to monitor brain activity by tracking blood flow, finding little evidence that long-term opioid use significantly altered brain anatomy. However, the study identified striking differences in how brain regions communicate, particularly within the mesocorticolimbic network—which governs reward and motivation—and the prefrontal cortex, which supports decision-making.
To analyze these patterns, the team developed a computational technique that integrated MRI data with published brain maps of neurotransmitter receptors. This method revealed distinct molecular signatures associated with chronic pain and opioid use, specifically involving serotonin and opioid receptors.
Developing Future Treatment Pathways
The research suggests that these molecular markers could guide the development of new treatments for chronic pain and opioid tapering. As part of the study, the team observed 21 patients who underwent a four-week pain rehabilitation program. Among these, eight patients reduced their opioid use by more than 30%, with their brain activity showing corresponding changes linked to the identified serotonin and opioid receptors.
Researchers now plan to test whether antidepressants that target these specific serotonin pathways can assist in managing chronic pain and reducing opioid dependence. "We identified molecular markers of different states of that brain in chronic pain patients," Apkarian said. These findings additionally offer direction regarding which novel therapies to investigate, the specific medications worth testing, and those that should be avoided.
Does Long-Term Opioid Use Cause Permanent Brain Damage?
Does long-term opioid use cause permanent brain damage?
The study found little evidence that years of low-to-moderate opioid use altered the brain’s anatomy. While researchers observed differences in how brain regions communicate, they did not find that the drugs caused the brain to "go crazy" or suffer structural deterioration.
How many people currently use prescription opioids for chronic pain?
Approximately 5 million U.S. adults use prescription opioids regularly to manage chronic pain. The Northwestern study, which was supported by the National Institutes of Health and the U.S. Department of Defense, represents the first research to examine both long-term opioid consumption and brain properties at this scale.
What is the next step for this research team?
The scientists intend to conduct clinical tests to see if antidepressants targeting the serotonin pathway can help patients manage chronic pain and successfully taper off opioids. This approach is based on the molecular signatures observed in patients who successfully reduced their opioid intake during a four-week rehabilitation program.
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