According to research presented this week at the American College of Rheumatology Annual Meeting in Washington, D.C., pain experienced by people with fibromyalgia may be caused by a problem with the way pain stimuli are processed in the brain. Abnormal pain signal processing may also be related to a lack of responsiveness to opioids, a common class of pain relievers.

Fibromyalgia is a common health problem that causes widespread pain and tenderness. An estimated five million Americans are affected by the disease, with co-occurring symptoms including chronic fatigue, cognitive problems, and poor sleep. Fibromyalgia is often difficult to diagnose and the condition is most common in women, though it can occur in men.

"Although we have known for some time that the brain is a key player in the pathology of fibromyalgia, we have yet to understand how pain regulation is disrupted in this condition," says Richard E. Harris, PhD, assistant professor at the University of Michigan, Ann Arbor, Mich., and lead investigator of the study.

Previous studies indicate that fibromyalgia patients have increased sensitivity to temperature, touch, and pressure. Moreover, some of Dr. Harris's previous work demonstrated that people with fibromyalgia produce an increased amount of endogenous opioid peptides (also known as endorphins that naturally relieve pain) that act on the brain's μ-opioid receptors to "naturally" reduce pain. Other work by this same group showed that the fibromyalgia brain displays an enhanced response to painful stimuli, suggesting a problem with pain processing. This current study sought to determine if these two factors, altered function of μ-opioid receptors and enhanced brain response to pain, actually occur simultaneously within the same group of people with fibromyalgia -- and within the same brain regions.

To answer this question, researchers from the University of Michigan measured the change in blood flow in the brains of 18 patients with fibromyalgia following a painful stimulus, using functional magnetic resonance imaging. They also measured the μ-opioid receptor binding availability with additional tests. These data were collected before and after acupuncture and sham acupuncture (which is essentially placebo acupuncture) treatment designed to reduce pain. The association between the brain's response to pain and the binding of μ-opioid receptors was then examined.

The study revealed a strong negative association between the brain's response to pain and the binding availability of μ-opioid receptors: the lower the receptor binding availability the greater the brain's response to pain. A positive correlation was also observed in a classic pain prevention region, the right dorsolateral prefrontal cortex. Importantly these associations were also related to the pain sensations patients reported.

For the first time, this study shows that μ-opioid receptor binding is tightly associated with the brain's response to pain in fibromyalgia. The data leads researchers to speculate that some individuals with fibromyalgia may have a down-regulation or decrease in opioid receptor activity that may exaggerate pain sensitivity. Moreover, these same individuals are likely to not benefit from opioid medications as they may have fewer functioning receptors.

"This data may also explain why some chronic pain states show similarities with paradoxical opioid-induced pain sensitivity," says Dr. Harris.

Funding for this study was provided by the National Institute of Health and the Department of Defense.