Figure 2 (above right) lists the classes of drugs and the level of evidence for their effectiveness in FM. In general, those drugs with the highest level of evidence of effectiveness in FM have also been shown to work in subsets of individuals with CSS. More importantly, drugs such as duloxetine are being shown to be effective in conditions such as osteoarthritis and low back pain, pointing out that the central mechanisms that are front and center in patients with syndromes such as FM may be also playing prominent roles in conditions previously thought to be peripheral pain syndromes. We have known for some time, however, that hyperalgesia and other central factors, as well as various other indicators of a wide range of “fibromyaglia-ness,” are present in conditions such as osteoarthritis and low back pain. It is of note that any one of these classes of drugs only works well in about a third of patients, which is entirely consistent that this is a strongly genetic—but polygenic— disorder and thus will need different treatments in different individuals. Going back to the “essential hypertension of pain processing pathway” analogy, just as we use eight to 10 classes of drugs acting in different body systems and at different molecular targets to control hypertension, and individuals may respond very well to one class of antihypertensive drug but not another, the same is true of CSSs. Individuals may only respond to one of these classes of drugs or may often be on several classes of centrally acting analgesics (e.g., a low dose of cyclobenzaprine at bedtime, pregabalin or gabapentin either just at bedtime or twice daily, and a serotonin– norepinephrine reuptake inhibitor such as duloxetine or milnacipran during the day). However, our current pharmacological armamentarium is not nearly as well developed for central pain as for essential hypertension, which is one likely reason that these syndromes are often difficult to treat.
Figure 2 also points out that classes of drugs such as NSAIDs and opioids that are quite effective for peripheral pain due to damage or inflammation in peripheral tissues are not effective analgesics in central pain states. There are even data suggesting that the use of opioids in individuals with central pain states may worsen their pain by leading to opioid-induced hyperalgesia that could augment and worsen the baseline hyperalgesia that may be playing a central pathogenic role in these conditions.
Just as many pharmacological therapies work across all or most of these conditions, similarly nonpharmacological therapies such as education, exercise, and cognitive behavioral therapy have been demonstrated to be effective across nearly all of the CSS conditions.42-44
Conclusion
In the past decades, our understanding of FM has evolved tremendously, and the study of FM has taught us about the mechanisms that may underlie chronic pain or other somatic syndromes in individuals without FM per se. A better understanding of the underlying mechanisms and most effective treatment for this spectrum of illness is critical to rheumatologists because, as Wolfe has taught us, many patients with rheumatic disorders have a little, or a lot, of “fibromyalgia-ness.” When this occurs, we need to treat both the peripheral and central elements of pain and other somatic symptoms.