Mechanistic Studies and Their Implication for the Management of Fibromyalgia Syndrome

Abstract

Objectives: To provide an overview of the findings regarding the underlying pathogenesis of FMSS and to compare these findings with the results of recent treatment studies to determine whether there is concordance between what “should work” and “what does” in this illness.

Findings: A number of different experimental modalities have been employed to demonstrate conclusively that FMSS is characterized by a “left-shift” in stimulus response function, that is, that FMSS patients display both hyperalgesia and allodynia. The fact that this occurs to several different types of sensory stimuli [pressure, heat or electricity applied to the skin, auditory stimuli] suggests that this augmented pain processing is primarily a central rather than peripheral process. There is additional evidence suggesting that there is a deficiency of descending analgesic activity in FMS, and that this is primarily due to decreased serotinergic/noradrenergic activity, rather than an inherent defect in opioid-induced analgesic systems. Additional evidence from experimental pain testing studies suggests that there is increased “wind-up” in FMS patients, reminiscent of the central sensitization due to increased glutamatergic and/or neurokinin activity noted in animal models. Finally, in addition to these neurobiological aberrations, it is well known that many individuals with FMS have or develop behavioral, psychological, and cognitive adaptations to their illness that may perpetuate or worsen symptoms.

In parallel, recent treatment studies have suggested that drugs that increase central serotinergic/noradrenergic activity [e.g., tricyclics, duloxetine, milnacipran, tramadol] or decrease levels of excitatory neurotransmitters [e.g., pregabalin, gabapentin] have been shown to have efficacy in FMS. Treatments that primarily address the behavioral, cognitive, or psychological comorbidities are also very effective.

Conclusions: Mechanistic studies reveal a number of neurobiological abnormalities in FMS that would be expected to lead to pain and/or sensory amplification, and clinical trials of drugs aimed at these targets have yielded the expected positive results. These trials suggest that different subgroups of patients may respond to different drugs, and that some patients may benefit from the concurrent use of education, cognitive-behavioral, and exercise programs that address comorbid problems often seen in FMS patients.

KEYWORDS:

• Fibromyalgia syndrome
• pain
• imaging
• treatment
• hyperalgesia