Brain Hyperactivation May Underlie Response to Pain in Fibromyalgia, Study Suggests

Brain Hyperactivation May Underlie Response to Pain in Fibromyalgia, Study Suggests
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The increased sensitivity to pain seen in people with fibromyalgia (FM) may be part of a more general high sensitivity — or brain hyperactivation — to other stimuli, or what neuroscientists call salient events, a study suggests.

These findings may indicate that medications and techniques that help to “reprioritize” these events —  such as “mindfulness meditation” that may help the body better cope with painful stimuli — may be useful in reducing FM symptoms.

The study, “Aberrant salience? Brain hyperactivation in response to pain onset and offset in fibromyalgia,” was published in the peer-reviewed journal Arthritis & Rheumatology.

Fibromyalgia is still a poorly understood condition, characterized by numerous symptoms, namely chronic musculoskeletal pain and mood and cognitive disturbances. The current consensus among scientists is that the disease is mainly a disorder of the central nervous system (CNS), manifesting with increased sensitivity to painful stimulus and a tendency for the body to perceive non-painful stimuli as painful.

“FM patients also show evidence of generalized hypersensitivity to visual, auditory, and olfactory stimuli,” the researchers said. “Given that FM patients appear to be hypersensitive to different types of sensory stimuli, we hypothesized that this increased sensitivity in response to noxious stimuli may partly reflect a more generalized hypersensitivity to salient sensory events.”

To find out, the researchers gave 38 FM patients and 15 healthy people (controls) mildly painful stimuli in their legs, and measured their brain responses via functional MRI (fMRI). Their responses to the onset and offset of pain were measured by tracking blood flow through their brains, a technique called BOLD (Blood-Oxygen Level Dependent) fMRI.

The BOLD signal increased in both FM patients and the healthy controls upon the introduction of pain. These increases occurred in largely the same areas, such as the frontal cortex, and other regions important for higher cognitive functioning. But the degree of activation was greater in the individuals with FM.

The participants with FM also showed activity in other regions that were not considered statistically significant.

A major difference occurred at the offset of pain. Here, FM patients showed activation in brain regions, while controls showed deactivation. The strongest effect occurred in the same higher cognitive functioning regions that saw activation during pain onset.

Although the heightened response to pain onset among FM patients was not unexpected, the differences at pain offset were. So was the magnitude of the response, particularly as the pain given to those with FM in this study was less than for the healthy controls.

“While an increased response to pain onset was not surprising, particularly given the extensive literature demonstrating overall stronger brain responses to pain stimuli in FM, the large group differences observed at pain offset were striking,” the researchers said.

These results were compatible with other data, such as information from self-report questionnaires, in which FM patients report greater sensitivity to everyday sounds and smells. In light of the brain pattern activity seen in this study, such sensitivity could be caused more by the changes in stimuli being experienced, than by their individual qualities.

The researchers argue that their data hints at “some sort of dysregulated modulatory processing” within the brains of people with fibromyalgia. If true, this raises the possibility that cognitive and behavioral therapy approaches, such as mindfulness meditation, might prove beneficial.

One notable finding was that the lateral prefrontal cortex (lPFC) showed the most responsiveness to both onset and offset of pain in FM patients. The lPFC is involved in many aspects of behavior control, and in particular, threat detection.

Another key finding was a strong association between fMRI signals in a behavior control center of the brain called the DLPFC and a phenomenon known as “pain catastrophizing.” With catastrophizing, the body believes it is experiencing a pain as much worse than it actually is.

This new finding supports previous studies that also found evidence linking catastrophizing and the DLPFC.

The degree of catastrophizing can predict whether or not a momentary acute pain develops into a chronic state of pain, that previous study had shown. The neurobiology underlying this connection remains poorly understood, however.

One theory is that catastrophizers cannot turn their attention away from their pain, which further sensitizes them to it and overwhelms their inhibitory mechanisms. That in turn leads to increasing attention on the pain experience.

By this theory, this feedback loop leads to pathological effects, such as pain amplification and pain responses to previously innocuous signals. That phenomenon is known as allodynic pain.

The researchers caution against drawing predictive conclusions from their study, as it did not control for medicine use, nor for behavioral features regarding the patients’ experience of salience.

Further studies also will need to examine whether the patterns of hyperactivity seen in people with FM also occur in other groups. Are these patterns seen, for instance, in pain-free people who also engage in catastrophizing?

Despite these caveats, the results of this study add important data to a growing body of research regarding the role of salience in fibromyalgia.

Forest Ray received his PhD in systems biology from Columbia University, where he developed tools to match drug side effects to other diseases. He has since worked as a journalist and science writer, covering topics from rare diseases to the intersection between environmental science and social justice. He currently lives in Long Beach, California.
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Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Técnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.
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Forest Ray received his PhD in systems biology from Columbia University, where he developed tools to match drug side effects to other diseases. He has since worked as a journalist and science writer, covering topics from rare diseases to the intersection between environmental science and social justice. He currently lives in Long Beach, California.
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