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Distinct Pain Signature Seen in People With Fibromyalgia

By Thomas G. Ciccone


Interview with Tor D. Wager, PhD

Historically, fibromyalgia (FM) lacks a definitive explanation for its underlying mechanisms of action,1 and has little consensus on objective, consistent physiological characteristics to define the condition for patients and physicians.2

Given the range of widespread, generalized symptoms, making a diagnosis of FM poses an ongoing challenge, despite its prevalence.3 Findings published in the journal Pain, offer valuable insight into the neurological underpinnings of FM.4

“I think looking at the brain can certainly be a clinical tool,” said Tor D. Wager, PhD, director of cognitive and affective neuroscience laboratory at the University of Colorado at Boulder.

“The challenge is finding well-defined targets,” Dr. Wager told Practical Pain Management. “It can kind of be like looking for a needle in a haystack.”

By mapping the neurological patterns seen in the brains of patients with FM researchers may be able to identify neural characteristics unique to this systemic condition, essentially create a “brain signature.”

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Mapping a Pain Signature for Fibromyalgia

In the mapping study, Dr. Wagner and his team assessed 37 female patients diagnosed with fibromyalgia and matched them to 35 healthy controls.

The researchers conducted a series of multisensory tests on participants to assess their sensory and motor responses. For instance, by using pressure stimulation tests, they examined how patients reacted to low and high forms of pressure pain.

The purpose of the study was to analyze how the brains of FM patients responded to different forms of stimuli, particularly pain. Using the neurologic pain signature (NPS),5 a brain pattern measured by functional magnetic resonance imaging (fMRI) was used to assess pain responses in humans.

Many regions referred to in the NPS are involved in nociceptive processing, such as the thalamus, which relays sensory and motor information to the cerebral cortex.

Other regions included in the NPS:

  • Secondary somatosensory regions (SI/SII)
  • Posterior, mid, and anterior insula
  • Adjacent opercula
  • Midbrain
  • Dorsal anterior cingulate cortex
  • Inferior frontal gyrus and amygdala

Hypersensitivity Detected in People With Fibromyalgia

The researcher team found that when FM patients were given a low-pressure form of pain stimulation, they reported much higher pain intensity in comparison to the control group, with a mean level of 71.71 ± 14.47 on the numerical rating scale versus 48.48 ± 18.31, respectively (between-group effect: t=5.95; P < 0.0005).4

The trend was similar with the outcome of unpleasantness, such that FM patients reported greater discomfort in response to low-pressure pain when compared to people without FM.4

In fact, the researchers found that when healthy controls were given high-intensity pressure pain, the controls’ responses were similar to that of FM patients who received low-intensity pressure pain.4 It’s a phenomenon characteristic of people suffering from FM,6,7 who typically report hypersensitivity to pain.

“This is consistent with what other groups have reported, and consistent with what patients are telling us—so in that sense, it’s not surprising,” said Dr. Wagner. “However, the difference is that this is the first time a brain measure that’s been extensively validated to be selective for evoked pain has been tested. So this strengthens the argument that there are at least a subset of FM patients with hypersensitivity to evoked pain.”

Indeed, when the researchers looked at how FM patients’ brain responded to low-intensity pressure pain compared to healthy controls receiving high-intensity pressure pain, they found the positive nociceptive response was virtually identical (t=0.07, P=0.94),4 similar to what they found with the patients’ subjective pain ratings.

Brain Responses in Patients With Fibromyalgia

By using a pattern recognition algorithm, the researchers were able to train a classifier to find other sets of brain features unique to patients who had FM. Many of these patients showed augmented activity in areas of the brain important for sensory integration, as well as self-referential, or default mode, areas of the brain.

Other regions of the brain were just as notable for their inactivity, like the dorsolateral prefrontal cortex, which is known to regulate pain and emotions.

According to Dr. Wager, these different brain features allowed researchers to create a system for classifying a brain of a patient with FM. The researchers even tested the validity of the brain map by correlating brain functioning patterns with clinical outcomes.

For instance, multiple regression analyses indicated that if patients had greater pain pattern responses related to FM and greater multisensory pattern responses, those patients suffered from greater clinical pain.

What Does the Future Hold?

According to Dr. Wager, finding these brain pathways signatures could help pain practitioners define the neurophysiological alterations, which may help explain the mechanisms driving FM. By developing a clearer understanding of the neurological mechanisms driving this disorder, the ability to make a diagnosis will become clearer, and targeted treatment more possible.

“This is a new idea in the neuroscience of FM, and it’s exciting that it may help us understand the multisensory sensitivity that many patients suffer from, and that it’s an important clue about the nature of this complex condition,” Dr. Wager told Practical Pain Management.

This research was supported in part by grants from the Ministry of Science and Innovation of Spain, by the by a Beatriu de Pinos postdoctoral fellowship. The authors declared no conflicts of interest.




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