CME

Improving Patient Outcomes in Fibromyalgia Syndrome: A Clinical Update on Appropriate Diagnosis, Adequate Treatment, and Proper Management of Comorbid Conditions

Daniel J. Clauw, MD

University of Michigan Medical School
Ann Arbor, Michigan

The questions below were submitted by your peers based on a recent CME activity.
The Course Director, Dr. Daniel J. Clauw, provides his answers below.

Question 1: Has anything been proven to decrease central sensitization (eg, using functional brain imaging)?

Question 2: Is pain following a mastectomy that hasn't gone away for years considered fibromyalgia?

Question 3: I've heard that viruses (ie, Epstein-Barr or murine leukemia virus-related virus) were found in patients with fibromyalgia. Is there any specific therapy linked to these viruses? Is anything known about a possible etiology from which these pathogens may give rise to the development of fibromyalgia?

Question 4: Is there a known pathophysiological explanation as to why pain medications like opioids and NSAIDs are not effective in patients with fibromyalgia but antidepressants and anticonvulsants are?

Has anything been proven to decrease central sensitization (eg, using functional brain imaging)?

There are several studies using functional neuroimaging before and after treatment of fibromyalgia with medications that suggest that elements of central sensitization are improved following therapy and associated with clinical improvements. For example, Guedj and colleagues used SPECT to show that when fibromyalgia patients were given ketamine, changes in midbrain (the brain region where many descending analgesic pathways originate) cerebral blood flow was correlated with improvements in pain [Guedj E et al. Eur J Nucl Med Mol Imaging. 2007;34(12):2115-2119]. Another group showed that treatment with amitriptyline reversed regions of hypoperfusion seen in fibromyalgia patients at baseline [Adiguzel O et al. South Med J. 2004;97(7):651-655].

Harris and colleagues have also performed studies suggesting that both “real” and sham acupuncture lead to improvements in clinical pain and pain threshold, and that these clinical improvements are related to reductions in glutamate levels in the posterior insula (another brain region consistently hyperactive in brain imaging studies in fibromyalgia) [Harris RE et al. Arthritis Rheum. 2008;58(3):903-907. Harris RE et al. Arthritis Rheum. 2009;60(10):3146-3152].

Is pain following a mastectomy that hasn't gone away for years considered fibromyalgia?

It is very possible if not likely that some of the pain experienced by women following mastectomy is “central” pain due to regional pain amplification—very similar to the underlying mechanism(s) of pain seen in fibromyalgia. Thus, it may respond to the same types of therapies as fibromyalgia. However, if the pain is not widespread, fibromyalgia would probably not be the most appropriate label to use to describe the pain.

I've heard that viruses (ie, Epstein-Barr or murine leukemia virus-related virus) were found in patients with fibromyalgia. Is there any specific therapy linked to these viruses? Is anything known about a possible etiology from which these pathogens may give rise to the development of fibromyalgia?

There are no studies that I am aware of that link any viruses to the pathogenesis of fibromyalgia. There are many studies suggesting that a variety of infections (eg, Epstein-Barr and parvovirus, Lyme spirochete) can trigger the subsequent development of fibromyalgia and/or chronic fatigue syndrome [Buskila D et al. Autoimmun Rev. 2008;8(1):41-43]. However, in these instances, there is no evidence that there is ongoing infection—but rather that infection is one of many stressors (including physical, immune, and emotional stressors) that seems to be capable of triggering these symptoms. Thus, it would not be appropriate to use antiviral therapies in these instances.

There is an emerging story regarding XMRV in chronic fatigue syndrome (CFS) [Lombardi VC et al. Science. 2009;326(5952):585-589]. A group has shown that CFS patients were much more likely to have evidence of this retroviral infection than a group of controls. However, these results need to be replicated before we conclude that there is an association between XMRV and CFS. Even then, it is very possible that this virus is not “pathogenic” but rather opportunistic, and thus it might be more likely to be present in individuals who have the subtle changes in immune function that are seen in conditions such as fibromyalgia and CFS but not be directly responsible for symptoms.

Is there a known pathophysiological explanation as to why pain medications like opioids and NSAIDs are not effective in patients with fibromyalgia but antidepressants and anticonvulsants are?

Yes. NSAIDs, and even opioids, seem to work much better for pain that is due to peripheral damage or inflammation (eg, acute pain due to trauma or surgery, conditions such as osteoarthritis) than pain that is due to central pain amplification, as is seen in fibromyalgia. In fibromyalgia, there are substantial data suggesting that neurotransmitters in the brain and spinal cord that are involved in pain transmission are abnormal (eg, high levels of Substance P and glutamate, low levels of serotonin and norepinephrine metabolites). Therefore, drugs that work to lower the activity of excitatory neurotransmitters or augment the activity of inhibitory neurotransmitters are the most effective classes of drugs.