Northwestern Study: Years of Opioid Use Do Not Improve Back Pain

Patients who took prescription opioids daily for an average of 7.8 years to manage chronic back pain reported essentially the same level of pain as closely matched patients who took none, according to a Northwestern University study published Oct. 1 in the journal Brain.

The research compared 70 long-term opioid users with 70 similar patients who were not taking opioids. Both groups rated their pain at about 5.4 on a 10-point scale. The opioid group did report slightly worse physical function and mental health, but the near-identical pain scores undercut the assumption that years of daily medication are buying meaningful relief — the reason most of these prescriptions continue to be written.

What the study measured

Beyond pain questionnaires, the Northwestern team used functional MRI to compare how the two groups' brains behaved at rest. Years of opioid use had left little mark on brain anatomy, which the researchers present as reassuring given how much is assumed about opioid-induced brain damage. The differences showed up instead in spontaneous activity — in the mesocorticolimbic network, a system tied to reward and motivation, and in the prefrontal cortex, which supports decision-making.

To interpret those patterns, the scientists built a computational technique that combined participants' MRI data with published maps of neurotransmitter receptors. That method produced distinct molecular signatures for different aspects of chronic pain and for long-term opioid use, with the differences involving serotonin and opioid receptors in the brain.

"For me, that's the most exciting part of the study," said A. Vania Apkarian, director of the Center for Translational Pain Research at Northwestern University Feinberg School of Medicine. "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."

The author's two-part message

Apkarian framed the findings as mixed news for the roughly 5 million American adults who take prescription opioids regularly for chronic pain. "The psychological and brain properties of the participants on long-term prescription opiates were essentially intact," he said. "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. 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."

He also stressed how the study was conducted. Participants in the opioid group were taking low or moderate doses under medical supervision, not the escalating doses or non-prescribed supply that define much of the overdose crisis, and Apkarian said this was the first study to look at long-term opioid consumption alongside brain properties. That distinction matters for how far the results travel: the paper describes stable, supervised patients in a research setting, not people who have developed opioid use disorder.

A serotonin lead for treatment

The molecular signatures point toward a specific next experiment. Because the markers implicated serotonin signaling, the Northwestern scientists plan to test whether an antidepressant that targets the same pathway can help treat chronic pain and support tapering off opioids.

They have a small hint already. Twenty-one patients in the study completed a four-week pain rehabilitation program, and eight of them cut their opioid use by more than 30 percent. Their brain activity shifted in ways linked to the serotonin and opioid receptors the researchers had flagged, adding evidence that the markers may someday help guide treatment decisions for both chronic pain and opioid reduction.

What the study cannot say

This was a comparison of two groups of 70 patients, not a randomized trial, so it cannot establish whether the drugs failed to help these patients or whether the patients who stayed on opioids for nearly eight years were different to begin with. It also did not track addiction, overdose or mortality outcomes, and it says nothing about how quickly or safely any individual patient should reduce a long-standing prescription.

The findings land in a policy environment where long-term opioid prescribing for chronic pain is already under pressure, but also where patients and clinicians have few well-evidenced alternatives. For those who have moved past supervised use into dependence, the evidence base points to medication for opioid use disorder rather than to tapering alone. The Northwestern work describes a different population and a different question: whether the prescription itself is doing what it is supposed to do. Its answer, at least for this cohort, is that it is not.