WASHINGTON -- The main pain inhibitory mechanisms in the brain may not function properly in fibromyalgia patients, researchers found.

Data from functional MRI (fMRI) and PET imaging studies suggest that the opioid system is involved in the pathogenesis of fibromyalgia, which may explain why some patients do not respond to, or experience worse symptoms with, narcotic analgesics, Richard Harris, PhD, of the University of Michigan in Ann Arbor, said in a presentation here at the American College of Rheumatology meeting.

Action Points This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

The main pain inhibitory mechanisms in the brain may not function properly in fibromyalgia patients.

Note that the findings imply that opioids may not be the best treatment option in these patients and may worsen their symptoms.

"We found that in fibromyalgia patients, the main pain inhibitory mechanisms are not working correctly, specifically, the opioid receptors within the brain," Harris told MedPage Today.

"What we found was somewhat paradoxical in that the fibromyalgia patients either have too few receptors in their brains, or the receptors themselves when they get activated are causing pain instead of [lessening] pain," he said.

For the study, conducted from 2008 to 2012, Harris and his colleagues recruited 18 female fibromyalgia patients who had never used opioids. Each participant underwent 4 weeks of nonpharmacological treatment. Before and after treatment, each patient underwent an fMRI scan with varying levels of pressure pain applied to the thumb.

The women also underwent a 90-minute PET scan under resting conditions. The researchers then analyzed the brain scans to determine which areas of the brain might be involved in the disease.

Clinical pain was assessed with the Short Form McGill Pain Questionnaire (SFMPQ).

The researchers found negative correlations between the change in the fMRI blood oxygenation level dependent (BOLD) signal and the mu-opioid receptor in multiple regions involved in pain processing and modulation, including:

Right posterior insula: R= -0.82 (P=0.0004)

Left medial insula: R= -0.82 (P=0.0003)

Left orbital frontal cortex: R= -0.75 (P=0.0004)

Right amygdala R= -0.68 (P=0.002)

They also found positive correlations in the right dorsolateral prefrontal cortex (R=0.66, P=0.003), the posterior cingulate (R=0.62, P=0.006), and the right putamen (R=0.72, P=0.0008).

Finally, changes in both functional imaging outcomes were negatively associated with changes in clinical pain:

BOLD in right dorsolateral prefrontal cortex and SFMPQ clinical pain: R= -0.52 (P=0.03)

Mu-opioid binding potential in left medial insula and SFMPQ present pain: R= -0.51 (P=0.03)

"The main result was that when opioid receptor binding went down, the evoked brain pain response went up in key brain regions that are involved in pain processing, such as the insula," Harris explained. "That could mean the receptors were getting down regulated. Alternatively, receptor binding potential can go down if there is a release of endogenous opioids which competes for the binding sites. If that is the case, then activation of the receptors is actually causing pain."

"Our findings indicate that there is tight regulation of the pain inhibitory systems in the brain, and in these patients it may be going awry," he added.

The findings imply that opioids may not be the best treatment option in these patients and may worsen their symptoms, Harris said.

Kathryn Dao, MD, from the Baylor Research Institute in Dallas said the study results add to the knowledge that "fibromyalgia in these patients does not respond well to narcotics. One of the reasons is that [these patients] have a high amount of endogenous opioids and a decreased amount of mu-opioid binding sites."

"Their receptors are overwhelmed already and they do not have receptors left to bind. These fibromyalgia patients are similar in this respect to patients who have chronic pain," explained Dao, who moderated the ACR press briefing where the results were presented.