Fibromyalgia: How the Brain Processes Pain and Opioids

by Karen Lee Richards Patient Advocate

According to research presented earlier this month at the American College of Rheumatology's Annual Meeting, the 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 help explain why some people with fibromyalgia do not respond well to treatment with opioids.

"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.

Accumulating Evidence

Previous studies, including other research done by Dr. Harris and colleagues, have taught us several things about FM pain.

  • People with FM have increased sensitivity to temperature, touch, and pressure.

  • People with FM 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.

  • 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 FM and within the same brain regions.

Study Design and Results

Researchers measured the change in blood flow in the brains of 18 patients with fibromyalgia following a painful stimulus, using functional magnetic resonance imaging (fMRI). 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 researchers 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 not likely to 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.

My Thoughts...

This is important research and helps to explain why FM pain can be so difficult to treat, particularly for the patients who have fewer functioning
µ-opioid receptors. For those people, treating their pain with opioids can actually increase their pain rather than relieving it.

My concern is that some physicians may generalize this study to include all FM patients. It has not yet been demonstrated that this applies to everyone with fibromyalgia and I hear from a lot of you for whom opioids have worked to reduce your FM pain. I hope doctors will treat each FM patient individually and be willing to try a variety of treatment options before ruling out any one class of medication.


Harris RE, et al. American College of Rheumatology (ACR) news release, Nov. 10, 2012.


Karen Lee Richards
Meet Our Writer
Karen Lee Richards

Karen is the co-founder of the National Fibromyalgia Association. She writes for HealthCentral as a patient expert for Pain Management.