Fibromyalgia - "Invisible" No longer

Fibromyalgia Can No Longer Be Called The "Invisible" Syndrome
November 4, 2008

Using single photon emission computed tomography (SPECT), researchers in France were able to detect functional abnormalities in certain regions in the brains of patients diagnosed with fibromyalgia, reinforcing the idea that symptoms of the disorder are related to a dysfunction in those parts of the brain where pain is processed.

"Fibromyalgia is frequently considered an 'invisible syndrome' since musculoskeletal imaging is negative," said Eric Guedj, M.D., and lead author of the study. "Past imaging studies of patients with the syndrome, however, have shown above-normal cerebral blood flow (brain perfusion) in some areas of the brain and below-normal in other areas. After performing whole-brain scans on the participants, we used a statistical analysis to study the relationship between functional activity in even the smallest area of the brain and various parameters related to pain, disability and anxiety/depression."

In the study, which was reported in the November issue of The Journal of Nuclear Medicine, 20 women diagnosed with fibromyalgia and 10 healthy women as a control group responded to questionnaires to determine levels of pain, disability, anxiety and depression. SPECT was then performed, and positive and negative correlations were determined.

The researchers confirmed that patients with the syndrome exhibited brain perfusion abnormalities in comparison to the healthy subjects. Further, these abnormalities were found to be directly correlated with the severity of the disease. An increase in perfusion (hyperperfusion) was found in that region of the brain known to discriminate pain intensity, and a decrease (hypoperfusion) was found within those areas thought to be involved in emotional responses to pain.

In the past, some researchers have thought that the pain reported by fibromyalgia patients was the result of depression rather than symptoms of a disorder. "Interestingly, we found that these functional abnormalities were independent of anxiety and depression status," Guedj said.

According to Guedj, disability is frequently used in controlled clinical trials to evaluate response to treatment. Because molecular imaging techniques such as SPECT can help predict a patient's response to a specific treatment and evaluate brain-processing recovery during follow-up, it could prove useful when integrated into future pharmacological controlled trials.

"Fibromyalgia may be related to a global dysfunction of cerebral pain-processing," Guedj added. "This study demonstrates that these patients exhibit modifications of brain perfusion not found in healthy subjects and reinforces the idea that fibromyalgia is a 'real disease/disorder.'"

According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases, fibromyalgia syndrome is a common and chronic disorder characterized by widespread muscle pain, fatigue and multiple tender points. Tender points are specific places - for example, on the neck, shoulders, back, hips, and upper and lower extremities - where people with fibromyalgia feel pain in response to slight pressure. The syndrome is one of the most common causes of musculoskeletal pain and disability and affects three to six million, or as many as one in 50, Americans. Between 80 and 90 percent of those diagnosed are women.

Although fibromyalgia is often considered an arthritis-related condition, it does not cause inflammation or damage to the joints, muscles or other tissues. Like arthritis, however, the significant pain and fatigue caused by fibromyalgia can interfere with a person's ability to carry out daily activities.

Coauthors of "Clinical Correlate of Brain SPECT Perfusion Abnormalities in Fibromyalgia" include Eric Guedj, Serge Cammilleri and Olivier Mundler, Service Central de Biophysique et de Médecine Nucléaire, AP-HM Timone; Jean Niboyet, Patricia Dupont, Eric Vidal and Jean-Pierre Dropinski, Unité d'Etude et de Traitement de la Douleur, Clinique La Phocéanne, all of Marseille, France.

About SNM: Advancing Molecular Imaging and Therapy

SNM is an international scientific and medical organization dedicated to raising public awareness about what molecular imaging is and how it can help provide patients with the best health care possible. SNM members specialize in molecular imaging, a vital element of today's medical practice that adds an additional dimension to diagnosis, changing the way common and devastating diseases are understood and treated.

SNM's more than 16,000 members set the standard for molecular imaging and nuclear medicine practice by creating guidelines, sharing information through journals and meetings and leading advocacy on key issues that affect molecular imaging and therapy research and practice.
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Why opioid pain killers don't work.

People who have the common chronic pain condition fibromyalgia often report that they don't respond to the types of medication that relieve other people's pain.

New research from the University of Michigan Health System helps to explain why that might be: Patients with fibromyalgia were found to have reduced binding ability of a type of receptor in the brain that is the target of opioid painkiller drugs such as morphine.

The study included positron emission tomography (PET) scans of the brains of patients with fibromyalgia, and of an equal number of sex- and age-matched people without the often-debilitating condition. Results showed that the fibromyalgia patients had reduced mu-opioid receptor (MOR) availability within regions of the brain that normally process and dampen pain signals -- specifically, the nucleus accumbens, the anterior cingulate and the amygdala.

Fibromyalgia patients had reduced mu-opioid receptor (MOR) availability within regions of the brain that normally process and dampen pain signals – specifically, the nucleus accumbens, the anterior cingulate and the amygdala.

"The reduced availability of the receptor was associated with greater pain among people with fibromyalgia," says lead author Richard E. Harris, Ph.D., research investigator in the Division of Rheumatology at the U-M Medical School's Department of Internal Medicine and a researcher at the U-M Chronic Pain and Fatigue Research Center.

"These findings could explain why opioids are anecdotally thought to be ineffective in people with fibromyalgia," he notes. The findings appear in The Journal of Neuroscience. "The finding is significant because it has been difficult to determine the causes of pain in patients with fibromyalgia, to the point that acceptance of the condition by medical practitioners has been slow."

Opioid pain killers work by binding to opioid receptors in the brain and spinal cord. In addition to morphine, they include codeine, propoxyphene-containing medications such as Darvocet, hydrocodone-containing medications such as Vicodin, and oxycodone-containing medications such as Oxycontin.

The researchers theorize based on their findings that, with the lower availability of the MORs in three regions of the brains of people with fibromyalgia, such painkillers may not be able to bind as well to the receptors as they can in the brains of people without the condition.

Put more simply: When the painkillers cannot bind to the receptors, they cannot alleviate the patient's pain as effectively, Harris says. The reduced availability of the receptors could result from a reduced number of opioid receptors, enhanced release of endogenous opioids (opioids, such as endorphins, that are produced naturally by the body), or both, Harris says.

The research team also found a possible link with depression. The PET scans showed that the fibromyalgia patients with more depressive symptoms had reductions of MOR binding potential in the amygdala, a region of the brain thought to modulate mood and the emotional dimension of pain.

The study subjects were 17 women with fibromyalgia and 17 women without the condition.

The senior author of the paper was Jon-Kar Zubieta, M.D., Ph.D., the Phil F. Jenkins Research Professor of Depression in the U-M Department of Psychiatry and a member of U-M's Molecular and Behavioral Neuroscience Institute, Depression Center and Department of Radiology. Other authors were Daniel J. Clauw, M.D.; David J. Scott, Ph.D.; Samuel A. McLean, M.D., MPH; and Richard H. Gracely, Ph.D.

Reference: The Journal of Neuroscience, Sept. 12, 2007, 27(37):10000--10006.
ScienceDaily (Oct. 3, 2007)