MARCH 22, 2016
Scientists from the United States and Australia have confirmed there is reduced gray matter volume in several areas of the brains of people who take opioids for more than a few days (Pain Med 2015 Dec 26. [Epub ahead of print]).
The researchers randomly assigned 11 people with low back pain to receive morphine daily for a month and another 10 to receive placebo. Subsequent imaging identified loss of gray matter in several reward- and pain-related regions of the brain in the morphine group but not the placebo group. There were no appreciable gray matter losses in the placebo group despite significant pain reduction.
The changes observed by the investigators corroborate evidence from an earlier study they published that showed alterations in the brain’s reward-related networks after one month of daily morphine use (Pain 2011;152:1803-1810).
“It’s disturbing to learn that in as little as one month, daily use of opioids can alter brain morphology. And it’s even more disturbing to learn that despite the harm caused to the subjects in the morphine arm, their pain wasn’t any better controlled than the patients receiving placebo,” commented Andrew Kolodny, MD, chief medical officer, Phoenix House; executive director, Physicians for Responsible Opioid Prescribing; and senior scientist, Heller School for Social Policy and Management, Brandeis University, Waltham, Mass. “This is strong evidence that for many patients, the risks of long-term opioids clearly outweigh potential benefit.”
However, lead investigator Joanne C. Lin, PhD, postdoctoral research fellow in the Department of Psychology at the University of Alabama at Birmingham, and her co-investigators from The University of Alabama; Stanford University, in California; and Monash University, in Victoria, Australia, said the study was small and that its clinical implications remain to be seen.
“It is important to note that brain changes do not necessarily mean that something bad has happened. The next step is to carefully monitor patients taking opioids to see what happens when the brain changes,” Dr. Lin said in an email to Pain Medicine News. “Are the brain changes associated with good (e.g., pain relief) or bad (e.g., addiction) outcomes? It is important that we answer that question before we start suggesting that this research should change how physicians treat pain.”
The patients’ average ages were 39 years in the morphine group and 45 years in the placebo group (P=0.178), and the average duration of pain was 11.1 years in the morphine group and 5.2 years in the placebo group (P=0.115). There was a 29.9% reduction in pain in the morphine group over the month of the study and a 33.3% reduction in the placebo group.
Magnetic resonance imaging revealed significantly reduced gray matter with morphine in the left inferior orbitofrontal cortex, right gyrus rectus, bilateral presupplementary motor areas and left dorsal posterior cingulate. There also was significant volume loss in the superficial subregions of the bilateral amygdala, left insula, two regions of the left superior temporal gyrus, right precentral gyrus, right superior frontal gyrus, right inferior temporal gyrus and right rolandic operculum. Several of these overlapped with decreases documented in earlier studies. There also were gray matter volume increases in some areas such as the bilateral insula and right hippocampus. There were no significant volume changes in placebo patients.
“I hope the authors report back on how these patients do over time. It will be important to learn if the brain changes are reversible after opioids are discontinued,” said Dr. Kolodny.
—Rosemary Frei, MSc