Juvenile fibromyalgia is associated with reduced volume in one region of the brain, according to a recent study. The findings were similar to those in patients with adult fibromyalgia, which suggests the importance of early diagnosis and treatment.
The study was published online January 25 in Arthritis and Rheumatology.
Adolescent Brain Development
Juvenile fibromyalgia is characterized by chronic widespread musculoskeletal pain that causes fatigue, sleep disorders, and mood disturbances — all of which have a tremendous impact on the adolescent’s academic performance and social activities. This disease is very challenging to diagnose. The onset of symptoms occurs at a critical period of brain development.
In a study conducted by the Pain and Emotion Neuroscience Laboratory (PENlab) at the School of Medicine and Health Sciences and the Institute of Neurosciences of the University of Barcelona in Spain, researchers analyzed the brain alterations associated with juvenile fibromyalgia. This study marks the first time that researchers have ever addressed these changes.
The researchers enrolled 34 adolescent girls with juvenile fibromyalgia and 38 healthy girls in their study. All participants underwent a structural MRI examination of the brain and were given a series of questionnaires to assess how much difficulty they had in carrying out daily activities. Using this information, the team analyzed different regions of the brain to determine whether gray matter volume (GMV) was larger or smaller in participants with fibromyalgia compared with those who did not have the disease. The team also examined whether the brain alterations accounted for the degree of pain, fatigue, and functional disability reported by the patients.
Reduced Gray Matter
“We found that gray matter volume reduction in the anterior midcingulate cortex is a common characteristic in girls with juvenile fibromyalgia as a group,” said lead author Marina López-Solà, PhD, assistant professor in the Department of Anesthesia at the University of Cincinnati. “That region of the brain is typically associated with acute pain processing. This finding could be related to excessive engagement of the nociceptive brain circuits and suggests a reorganization of these circuits. In addition, the presence of this alteration in girls and women with fibromyalgia suggests that there’s a link between juvenile and adult forms of the disease.”
The study also found that in the patients who were most affected by the disease and who had more symptoms, there was an increase in GMV in frontal regions that are linked to affective, self-referential, and language-related processing. “While further research would be needed to confirm, it seems that these alterations could reflect an alteration in the development of the frontal circuits that are involved in emotional appraisal and regulation and in narrative/language processing,” said Maria Suñol, PhD, a postdoctoral researcher at the University of Barcelona.
Pain and the Brain
The past two decades have seen exponential growth in research in which neuroimaging is used to study adult fibromyalgia. There is now robust evidence that chronic pain symptoms are related to alterations involving a multitude of brain circuits and functional domains beyond those typically associated with nociceptive processing. “For example, in previous studies, our group found that adult women patients present with alterations in the processing of nonpainful sensory stimuli (when confronted with loud sounds or high-contrast bright images) or in regions that process emotions or self-referential thoughts,” said López-Solà.
López-Solà and Suñol can’t say for certain whether these alterations are the cause or the consequence of fibromyalgia. They believe there is a need for more longitudinal studies with follow-up of the patients, as well as studies involving asymptomatic individuals who are at high risk of developing the disease. “If we want to get to know the pathophysiological causes of fibromyalgia, it’s essential that we look at how the condition affects recently diagnosed young people who haven’t shown symptoms and haven’t been on pharmacological treatment for any great length of time,” said López-Solà. “With respect to this, we’ve seen that, apart from the GMV reduction in the anterior midcingulate cortex, symptoms such as fatigue or the difficulty that participants experience when carrying out their daily activities are linked to inferior frontal alterations. In other words, different symptoms seem to be associated with different brain circuits.”
López-Solà and Suñol said they are working on analyzing how the brains of these patients respond to specific stressful stimuli, including pressure pain, nonpainful multisensory stimulation, and opinion of their own way of being. “In this way, we hope to better understand how brain activity could be altered in juvenile fibromyalgia.”
That there is a relationship between fibromyalgia and abnormal functioning of the central nervous system has been known for a few years now. This seems to have been already established in the case of adult fibromyalgia. Is this relationship true of juvenile fibromyalgia as well? In Suñol’s opinion, “This study’s results suggest that even in recently diagnosed girls, there are changes in the structure of the brain, regardless of how long these patients have been experiencing symptoms. In addition, we’ve found that some of the changes seen in girls with juvenile fibromyalgia precisely match up with those identified in adult women who have the same disease, according to previous meta-analyses. These changes that we see in both groups are located in the same place: the anterior midcingulate cortex and posterior cingulate cortex, regions having to do with pain, autobiographical memory, and mentalization, which is the ability to understand the mental state of oneself or others.”
A Challenging Diagnosis
Evaluating fibromyalgia is challenging because there are no definitive and specific laboratory tests to diagnose the disease. When it comes to understanding the clinical complexities of fibromyalgia, physicians mostly look to the patient’s symptoms. “Taking this approach, the doctor may not get a complete picture of what’s actually going on,” said Suñol. “And as a result, the patient may be given treatments that aren’t as effective as they could be. In addition, there’ve been questions as to whether a clinical diagnosis of juvenile fibromyalgia can be made. Indeed, sometimes the symptoms are just viewed as being signs of anxiety or depression.”
The 2020 updated protocols of the Spanish Association of Pediatric Rheumatology provide a set of diagnostic criteria for juvenile fibromyalgia. Some of the salient criteria are the presence of generalized pain in at least three areas of the body for more than 3 months, the absence of an underlying condition or cause that could explain the symptoms, normal laboratory tests, and pain on at least five of the 18 tender point sites. “Therefore, the first step is to carry out tests so that we can rule out other diseases or causes that could explain the symptoms. Once they’ve been ruled out, a rheumatologist who specializes in juvenile fibromyalgia should be consulted for a diagnosis,” said López-Solà. She went on to say, “Although there are rheumatology departments with staff that stays up to date about this disease, the overload of cases in the primary care setting sometimes prevents these clinicians from taking the kind of specialized approach that’s required to treat these patients. These days, there’s still a stigma attached to juvenile fibromyalgia. So, we look to research, which we believe can play a key role when it comes to showing that fibromyalgia is associated with specific neurophysiological alterations.”
As to using her team’s findings in clinical practice, Suñol commented, “They reinforce the need to combine pain-specific sensory therapies with therapies aimed at promoting cognitive regulation of pain, negative affect, and potentially pervasive self-related narratives patients may hold of themselves.” However, because this was the first study to analyze the brain changes associated with juvenile fibromyalgia, “it’s impossible to directly translate our results into clinical practice. For that, the brains of these patients have to be looked at from multiple perspectives, analyzing not only the structure but also the functioning of the brain both when it’s at rest and when it’s faced with painful, cognitive, and emotional stimuli. Similarly, to draw robust conclusions, it’s necessary to replicate our results in patient samples that are larger and more diverse in terms of ethnicity, culture, and socioeconomic status.”
In conclusion, López-Solà noted, “We’ve taken a very important first step, but we know it’s not enough. That’s why we’re extremely motivated to continue moving in this direction — especially in the development of disease biomarkers and in the classification of patient subtypes, which could prove to be useful both for detecting and for treating fibromyalgia in a more personalized way.”
Arthritis Rheumatol. Published online January 25, 2022. Abstract