The primary symptom of fibromyalgia (FM) is chronic, widespread pain; however, patients report additional symptoms including decreased concentration and memory. Performance based deficits are seen mainly in tests of working memory and executive function. Neural correlates of executive function were investigated in 18 FM patients and 14 age-matched HCs during a simple go/no-go task (response inhibition) while they underwent functional magnetic resonance imaging (fMRI). Performance was not different between FM and HC, in either reaction time or accuracy. However, fMRI revealed that FM patients had lower activation in the right pre-motor cortex, supplementary motor area (SMA), mid cingulate cortex (MCC), putamen and, after controlling for anxiety, in the right insular cortex (IC) and right inferior frontal gyrus (IFG). A hyper-activation in FM patients was seen in the right inferior temporal gyrus/fusiform gyrus. Despite the same RTs and accuracy, FM patients show less brain activation in cortical structures in the inhibition network (specifically in areas involved in response selection/motor preparation) and the attention network along with increased activation in brain areas not normally part of the inhibition network. We hypothesize that response -inhibition and pain perception may rely on partially overlapping networks, and that in chronic pain patients resources taken up by pain processing may not be available for executive functioning tasks such as response inhibition. Compensatory cortical plasticity may be required to achieve performance on par with control groups.
Chronic pelvic pain (CPP) is a highly prevalent pain condition, estimated to affect 15-20% of women in the United States. Endometriosis is often associated with CPP, however other factors, such as pre-existing or concomitant changes of the central pain system, might contribute to the development of chronic pain. We applied voxel-based morphometry to determine whether women with CPP with and without endometriosis display changes in brain morphology in regions known to be involved in pain processing.Four subgroups of women participated: 17 with endometriosis and CPP, 15 with endometriosis without CPP, 6 with CPP without endometriosis, as well as 23 healthy controls. All patients with endometriosis and/or CPP were surgically-confirmed. Relative to controls, women with endometriosis-associated CPP displayed decreased gray matter volume in brain regions involved in pain perception including the left thalamus, left cingulategyrus, right putamen, and right insula. Women with CPP without endometriosis also showed decreases in gray matter volume in the left thalamus. Such decreases were not observed in patients with endometriosis that had no CPP. We conclude thatCPP is associated with changes in regional gray matter volume within the central pain system. Although endometriosis may be an important risk factor for the development of CPP, acting as a cyclic source of peripheral nociceptive input, our data support the notion that changes in the central pain system also play an important role in the development of chronic pain, regardless of the presence of endometriosis.
The insular (IC) and cingulate cortices (CC) are critically involved in pain perception. Previously we demonstrated that fibromyalgia (FM) patients have greater connectivity between the insula and Default Mode Network at rest, and that changes in the degree of this connectivity were associated with changes in the intensity of ongoing clinical pain. Here we more thoroughly evaluate the degree of resting state connectivity to multiple regions of the IC in individuals with FM and healthy controls (HC). We also investigated the relationship between connectivity, experimental pain and current clinical chronic pain. Functional connectivity was assessed using resting state functional magnetic resonance imaging in 18 FM patients and 18 age- and sex-matched HC using pre-defined seed regions in the anterior, middle and posterior IC. FM patients exhibited greater connectivity between: (1) right mid IC and right mid/posterior CC and right mid IC; (2) right posterior IC and the left CC; and (3) right anterior IC and left superior temporal gyrus. HCs displayed greater connectivity between: left anterior IC and the bilateral medial frontal gyrus/ACC; and left posterior IC and the right superior frontal gyrus. Within the FM group, greater connectivity between the IC and CC was associated with decreased pressure-pain thresholds. Perspective These data provide further support for altered resting-state connectivity between the IC and other brain regions known to participate in pain perception/modulation playing a pathogenic role in conditions such as FM. We speculate that altered IC connectivity is associated with the experience of chronic pain in individuals with fibromyalgia.
Fibromyalgia is a chronic pain syndrome characterized by widespread pain, fatigue, and memory and mood disturbances. Despite advances in our understanding of the underlying pathophysiology, treatment is often challenging. New research indicates that changes in functional connectivity between brain regions, as can be measured by magnetic resonance imaging (fcMRI) of the resting state, may underlie the pathogenesis of this and other chronic pain states. As such, this parameter may be able to be used to monitor changes in brain function associated with pharmacological treatment, and might also be able to predict treatment response.We performed a resting state fcMRI trial using a randomized, placebo-controlled, cross-over design to investigate mechanisms of action of milnacipran (MLN), a selective serotonin and norepinephrine reuptake inhibitor (SNRI), in fibromyalgia patients. Our aim was to identify functional connectivity patterns at baseline that would differentially predict treatment response to MLN as compared to placebo. Since preclinical studies of MLN suggest that this medication works by augmenting antinociceptive processes, we specifically investigated brain regions known to be involved in pain inhibition.15 fibromyalgia patients completed the study, consisting of 6 weeks of drug and placebo intake (order counterbalanced) with an interspersed 2 week wash out period. As a main finding we report that reductions in clinical pain scores during MLN were associated with decreased functional connectivity between pro-nociceptive regions and antinociceptive pain regions at baseline, specifically between the rostral part of the anterior cingulate cortex (ACC) and the insular cortex (IC), as well as between the periaqueductal gray (PAG) and the IC: patients with lower preexisting functional connectivity had the greatest reduction in clinical pain. This pattern was not observed for the placebo period. However a more robust placebo response was associated with lower baseline functional connectivity between the ACC and the dorsolateral prefrontal cortex.This study indicates that ACC–IC connectivity might play a role in the mechanism of action of MLN, and perhaps more importantly fcMRI might be a useful tool to predict pharmacological treatment response.
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