Comorbid Insomnia Exacerbates Fibromyalgia Brain Changes

Clinical Pain Advisor
December 21, 2015

Michael O’Leary

Comorbid insomnia exacerbates fibromyalgia-related alterations in the default mode network (DMN), according to a novel clinical neuroimaging study published in Journal of Pain Research.¹

Researchers led by Christina S. McCrae, PhD, from the University of Missouri in Columbia, MO, used functional MRI (fMRI) to study brain activity in the intervals between applications of heat stimuli to the sole of the foot. The study population included 39 women with fibromyalgia and comorbid insomnia; 13 women with fibromyalgia alone served as controls.


Results showed that patients with clinically disordered sleep due to comorbid insomnia had significantly more DMN activity during stimulus-free intervals than those with fibromyalgia alone. Also known as the task-negative network because of its activity during rest, the DMN includes the right cingulate gyrus, medial prefrontal gyrus, left inferior parietal lobule, and the left anterior cingulate.

The findings confirmed researchers' expectations that comorbid disease states have an additive effect on brain function.

"Either one of these [conditions] alone is associated with disrupted brain functioning, but putting them together [shows] there is not only overlap of both diagnoses, but you seem to get an exacerbated or elevated dysfunction,"coauthor Jason Craggs, PhD, assistant professor at the University of Missouri  School of Health Professions in Columbia, MO, told Clinical Pain Advisor.

Although chronic pain alone previously was associated with altered DMN activity, the impact of comorbidities was difficult to ascertain before the advent of functional neuroimaging, Dr. Craggs pointed out.

Functional neuroimaging helped us tease apart and identify inter-group differences in brain activity that matched our expectations based on behavioral observations, Dr. Craggs said.

The study was part of a larger effort investigating the mechanisms underlying comorbid fibromyalgia and insomnia, and the potential benefit of cognitive-behavioral interventions for sleep and pain.

Additional Brain Areas Involved
Prior to the neuroimaging protocol, participants underwent a single night of ambulatory polysomnography and were instructed to keep a sleep diary each morning for 14 days.

A computer-controlled Medoc Thermal Sensory Analyzer was then used to deliver 4 functional runs, each lasting approximately 5 minutes, and spaced 2 minutes apart.

Each run included an initial 40-second task-negative period, followed by 3 cycles of alternating 30/60-second task-oriented and task-negative periods, and ended with a 60-second task-negative period. Task-oriented periods consisted of eight 1-second thermal pulses, ranging from warm to painful, delivered under the ball of the right foot.

Functional MRI was used to image brain activity during task-oriented and task-negative periods. To minimize error, researchers used a combination of statistical significance (P ≤ .03) and minimum cluster size (135 µL) to establish the probability of a false positive at 0.0007. The statistical parameter maps were then overlaid on a standardized 3D anatomical volume for localization.

"While in the scanner, they were exposed to a thermal stimulus — a painful heat pulse. However, the analyses focused on task-negative periods — what the brain was doing in between those stimuli — to establish a baseline function of the brain when it is not doing a task," Dr. Craggs explained.

Results showed that clinically disordered sleep significantly contributed to group differences in areas both inside and outside the DMN, including the right cingulate gyrus, left lentiform nucleus, left anterior cingulate, left superior gyrus, median frontal gyrus, right caudate, and the left inferior parietal lobules.

According to the authors, recruitment of additional brain regions during task-negative periods may signal reorganization of the DMN.

Treat Both Insomnia and Pain

Although the study did not evaluate treatments, the findings indicate that treating both comorbid conditions may be more effective than treating either one alone, senior investigator Christina McCrae, PhD, chair of the department of health psychology at the University of Missouri School of Health Professions, told Clinical Pain Advisor.

"It used to be thought that if you had a chronic pain condition and sleep problems, the sleep problems were just part of the pain condition. Now there is thinking that not only are the conditions reciprocal, but there is a strong interest in the idea that if you can directly treat the sleep you might see some impact on pain," Dr. McCrae pointed out.

"We know that there is disrupted brain activity and that the disruption is worse for people with a comorbid diagnosis. We don't have a specific targeted treatment to hand off to clinicians yet — that is what we are currently researching. What we do know is that if you combine your treatments it is best to be mindful of both disorders and try to address both in your treatment rather than focus on one or the other," Dr. Craggs concurred.

Future research is planned to determine the impact of cognitive behavioral therapy on disrupted areas of the brain in patients with insomnia and chronic pain conditions.

"The ultimate goal of our work is to look at the impact of different treatments — alone and possibly combined — on what is happening within the brains of these patients, because our overarching hypothesis is that chronic pain and insomnia share a common underlying nervous system mechanism," Dr. McCrae concluded.

Reference

Vatthauer KE, Craggs JG, Robinson ME. Sleep is associated with task-negative brain activity in fibromyalgia participants with comorbid chronic insomnia. J Pain Res. 2015 Nov 12;8:819-27. doi: 10.2147/JPR.S87501. eCollection 2015.