Pain 101: Looking to the Brain to Understand Fibromyalgia and Other Chronic Pain Conditions

Fibromyalgia and the brain

The idea of “FM-ness” is helping doctors to diagnose patients and come up with effective treatment strategies. Image credit: xstudio3d/123RF Stock Photo.

Editor’s Note: The second North American Pain School (NAPS) took place June 25-29, 2017, in Montebello, Quebec, Canada. This educational initiative brought together leading experts in pain research and management to provide 30 trainees–part of the up-and-coming generation of pain researchers–with scientific education, professional development and networking experiences. Six of the trainees were also selected to provide first-hand reporting from the event, including summaries of talks presented at the meeting. Here, Jessica Ross, who recently completed her PhD at the University of Cincinnati, summarizes a talk delivered by Daniel Clauw, a rheumatologist at the University of Michigan. Clauw’s talk described a new way of thinking about fibromyalgia and related pain conditions.

Daniel Clauw, a doctor and clinical researcher at the University of Michigan, wants to change the way we think about and treat chronic pain. As a practicing rheumatologist—a joint and autoimmune disease specialist—Clauw has been at the forefront of understanding how chronic pain conditions develop and establishing effective treatments. His recent research, described during a talk at the North American Pain School, has focused on the contribution of the central nervous system (CNS; brain and spinal cord) to a number of chronic pain conditions, including fibromyalgia (FM).

Clauw and colleagues have developed the idea of “FM-ness,” a scale providing an indication of the degree to which the CNS plays a role in a patient’s pain. The more FM symptoms patients experience, the higher their score on the scale. With every increase of this score, it becomes more likely that the CNS is the driver of their chronic pain and less likely that they will respond to certain treatments. The idea is that FM symptoms occur over a continuum, rather than being present or absent. Knowing a patient’s score may then help physicians to better determine the best therapies to treat not only FM but also a variety of painful conditions.

A better way to diagnose fibromyalgia
Clauw first became interested in muscle pain disorders (myalgias) when he helped to describe a new disease in 1992 that caused skin and nerve damage, along with the sudden onset of severe pain. That disease is known as eosinophilia-myalgia syndrome (EMS).

Hundreds of people developed the condition in the late 1980s, which was linked to the use of a contaminated dietary supplement called L-tryptophan (the precursor to the neurotransmitter serotonin). This led to a temporary (until 2005) ban of the product in the United States. Clauw saw that many of the individuals with EMS developed symptoms similar to those with FM, who show a lack of energy, chronic widespread pain, and changes in mood, sleep, and memory.

Until recently, many doctors were reluctant to consider FM a true disease, viewing it as a psychosomatic condition—that it was “all in the head.” The initial guidelines for a diagnosis of FM, promoted in 1990 by the American College of Rheumatology (ACR; a professional organization of healthcare professionals and scientists in the field of rheumatology), perhaps contributed to this misconception.

That is, according to the criteria, for doctors to say whether or not a person had FM, after ruling out other potential diagnoses, a test of “tender points” was the gold standard. Here, pressure was applied to nine predefined sites on both sides of the body (18 in total), and only patients with pain in at least 11 of these areas would be diagnosed with FM. The rationale for this test was that FM, at its core, is a disorder causing chronic pain throughout the body, so if pressure was found to be painful at multiple sites, a patient would be more likely to have this disorder.

However, this approach was found to have a number of issues that prevented it from accurately identifying patients with FM. For example, with the assessment of tender points, women were more likely to rate the pressure as painful, across multiple sites, than men were. This may have led to a disproportionate number of women being diagnosed with FM, and potentially ignored male patients with the disease who showed ten or fewer painful sites at the time of the exam. In addition, specific painful sites in an FM patient can differ between testing days. And, differing testing approaches between medical providers could also limit the ability to detect disease.

For all of these reasons, the ACR revised its criteria for the diagnosis of FM in 2010. Clauw and his colleagues wrote these updated criteria, which incorporate measures of time (Have symptoms been ongoing for at least three months?), of where the pain is (In how many areas is pain occurring? Is it widespread?), and how bad the symptoms are (including pain as well as sleep, mood, and memory problems). These criteria allow doctors to assess many different aspects of a patient’s life that can be disrupted by FM, which helps them to reach a diagnosis.

All eyes on the central nervous system
As a physician, Clauw has often seen FM-like widespread pain, fatigue, memory problems, mood issues, and sleep disturbances in patients with other disorders, such as knee osteoarthritis, but who do not meet the criteria for a diagnosis of FM. And, FM-like symptoms could persist even when the underlying condition was treated successfully.

As a result, Clauw too began to question if FM symptoms were “all in the head,” but from a fresh perspective. Maybe the painful symptoms of FM were not due to problems starting in the muscles or the skin, but rather to changes in how the CNS processes pain.

For example, someone who breaks an arm can be expected to have pain around the area where the bone was broken. Typically, once the bone heals, the pain fades away. Interestingly, some people might show severe damage to the bone or neighboring joint on an x-ray but still not experience prolonged pain. But if the pain continues, gets stronger, or even begins to cover the entire arm, those individuals may have CNS involvement in their pain (centralized pain).

The more locations in which a person has pain, the more likely it is that the CNS is involved. Intriguingly, psychological and social factors thought to enhance pain sensitivity, such as anxiety and depression, explain very little of the differences seen between patients with and without centralized pain.

To explain the idea of centralized pain, Clauw uses a musical metaphor:

Consider the loudness of an electric guitar to represent the amount of pain a person is experiencing. Like the strings of a guitar, there are many types of sensory nerves that produce qualitatively different kinds of sensory information from the skin, muscle, and joints, but in order to hear this information, it has to be processed through an amplifier, the central nervous system. So you can get someone to have more pain by strumming the individual strings of the guitar harder and faster, but another way to increase the loudness would be to turn up the amplifier. And by increasing the level of the amplifier, all strings become louder.

Thinking of the CNS as an amplifier of pain signals helps to explain why people with similar levels of inflammation and/or tissue damage from injury or disease may have very different pain levels—the strength of the amplifier differs. When the amplifier is dialed up too high, the result is centralized pain.

Patients who show changes in the CNS have pain that differs from the pain typically caused by injury in that it is more extensive and can spread from one part of the body to another. In fact, it has recently been shown that some regions of the brain that process sensory input from the body can increase in size as pain becomes more widespread.

“FM-ness” as a way to think about pain more broadly
What else have researchers learned using the concept of “FM-ness”? Clauw has looked to a different set of patients to learn more—those with osteoarthritis (OA) of the knee or hip.

Clauw and his team used a number of surveys, including FM assessments, in a group of knee and hip OA patients prior to joint replacement surgery, and followed how they did after surgery. For this 2015 study, the group hypothesized that patients with higher FM scores, and therefore presumably greater levels of CNS involvement in pain, would experience less pain relief after surgery. Although some of the patient volunteers in this study were found to meet the criteria for FM diagnosis, they were not included in the researchers’ analysis. Instead, the study focused on OA patients who had some symptoms of FM, but not enough to be diagnosed with it.

And indeed, in these patients, the higher their FM scores were, the less their pain improved after surgery. Other studies have shown that those with more FM-like symptoms use greater amounts of opioids to control their pain, and also take longer to recover from surgery.

Clauw believes the idea of “FM-ness” is a useful way to understand pain that occurs in a variety of chronic pain conditions, even in patients who do not meet the criteria for a diagnosis of FM. It helps physicians gain a sense of the involvement of the CNS in pain and better determine how their patients will fare.

From centralized pain to treatment
Perhaps the most important reason to describe the level of CNS involvement in pain is to figure out effective treatment strategies. For example, Clauw said that physicians are often taught that knee pain comes from the knee. However, pain that is more centralized may not respond to typical knee pain treatments such as ibuprofen or opioids. In fact, drugs for epilepsy or depression do a better job of working in the CNS and have more positive effects in centralized pain states, even at very low doses.

Non-drug therapies are also important to manage centralized pain. Treatment plans including yoga, tai chi, meditation, cognitive behavioral therapy, and mild voluntary exercise regimens may be much better for these patients than drugs. These approaches may ultimately be more successful at treating the lingering or widespread pain occurring after the initial course of treatment is complete. Although putting a broken arm in a sling or replacing an arthritic knee may be important for managing pain, they are not the whole story.

It is critical, then, to understand how much the CNS is involved—how strong is the amplifier? Using the idea of “FM-ness” might give physicians a better handle on how to approach chronic pain—not just in FM but in a variety of painful conditions—and allow for the most effective course of treatment.

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