Increased brain gray matter in the primary somatosensory cortex is associated with increased pain and mood disturbance in patients with interstitial cystitis/painful bladder syndrome.

PURPOSE: Interstitial cystitis is a highly prevalent pain condition estimated to affect 3% to 6% of women in the United States. Emerging data suggest there are central neurobiological components to the etiology of this disease. We report the first brain structural imaging findings from the MAPP network with data on more than 300 participants. MATERIALS AND METHODS: We used voxel based morphometry to determine whether human patients with chronic interstitial cystitis display changes in brain morphology compared to healthy controls. A total of 33 female patients with interstitial cystitis without comorbidities and 33 age and gender matched controls taken from the larger sample underwent structural magnetic resonance imaging at 5 MAPP sites across the United States. RESULTS: Compared to controls, females with interstitial cystitis displayed significant increased gray matter volume in several regions of the brain including the right primary somatosensory cortex, the superior parietal lobule bilaterally and the right supplementary motor area. Gray matter volume in the right primary somatosensory cortex was associated with greater pain, mood (anxiety) and urological symptoms. We explored these correlations in a linear regression model, and found independent effects of these 3 measures on primary somatosensory cortex gray matter volume, namely clinical pain (McGill pain sensory total), a measure of urgency and anxiety (HADS). CONCLUSIONS: These data support the notion that changes in somatosensory gray matter may have an important role in pain sensitivity as well as affective and sensory aspects of interstitial cystitis. Further studies are needed to confirm the generalizability of these findings to other pain conditions.

Mind the Mood: Momentary Depression and Anxiety Moderate the Correspondence Between Subjective and Objective Cognitive Functioning in Fibromyalgia.

OBJECTIVE: Subjective cognitive dysfunction (SCD) affects 55-75% of individuals with fibromyalgia (FM), but those reporting cognitive difficulties often lack corresponding objective deficits. Symptoms of depression and anxiety are prevalent in FM and may account for part of this discrepancy. This study was undertaken to investigate whether momentary (within-day, across 7 days) changes in mood moderate the relationship between within-the-moment SCD and mental processing speed performance. METHODS: A total of 50 individuals with FM (mean age 44.8 years, mean education 15.7 years, 88% female, 86% White) completed momentary assessments of subjective cognitive functioning, depressive and anxious symptoms, and a test of processing speed. Assessments were completed 5 times per day for 8 consecutive days on a study-specific smartphone application. RESULTS: Momentary ratings of SCD were positively associated with mean reaction time (P < 0.001) and variability of processing speed (P = 0.02). Depressive symptoms moderated the relationship between SCD and processing speed, with lower correspondence when depressive symptoms were higher (P = 0.03). A similar moderating effect was demonstrated for both depression (P = 0.02) and anxiety (P = 0.03) on the association between SCD and variability in processing speed performance. CONCLUSION: Individuals with FM may have more accurate self-perception of momentary changes in mental processing speed during periods of less pronounced mood symptoms based on their corresponding objective processing speed performance. However, during moments of heightened depression and anxiety, we found increasingly less correspondence between SCD and objective performance, suggesting that psychological symptoms may play an important role in self-perception of cognitive dysfunction in FM as it relates to mental processing speed.

Association of Alterations in Gray Matter Volume With Reduced Evoked-Pain Connectivity Following Short-Term Administration of Pregabalin in Patients With Fibromyalgia.

OBJECTIVE: Pregabalin (PGB) is an α2 δ calcium-channel subunit ligand that has previously been shown to reduce chronic pain in multiple conditions. Preclinical studies indicate that PGB may down-regulate brain glutamate release while also inhibiting astrocyte induction of glutamatergic synapse formation, and recent clinical findings support the notion that PGB modulates glutamatergic activity and functional brain connectivity in order to produce analgesia. The present study was undertaken to examine concurrent changes in brain gray matter volume (GMV) or evoked-pain connectivity in humans receiving PGB. METHODS: Sixteen female fibromyalgia patients participated in a randomized double-blind 2-period crossover study of PGB versus placebo. Before and after each period, patients underwent high-resolution structural and evoked pressure-pain functional brain imaging. GMV was analyzed using voxel-based morphometry, and functional connectivity during evoked pressure-pain was assessed. RESULTS: PGB administration significantly reduced GMV within the posterior insula bilaterally, whereas there were no significant changes in insular GMV following placebo treatment. GMV reductions in the medial frontal gyrus were also observed when comparing PGB versus placebo treatment, and were associated with reduced clinical pain. These reductions in insular GMV were associated with concomitant reductions in connectivity to the default mode network, which was also associated with reduced clinical pain. CONCLUSION: Short-term PGB treatment altered brain structure and evoked-pain connectivity, and these decreases were associated with reduced clinical pain. We speculate that these fairly rapid changes in GMV may be related to brain neuroplasticity. It is unknown whether these effects are generalizable to other chronic pain states.

Altered resting state connectivity of the insular cortex in individuals with fibromyalgia.

UNLABELLED: The insular cortex (IC) and cingulate cortex (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. In this study we more thoroughly evaluated the degree of resting-state connectivity to multiple regions of the IC in individuals with FM and healthy controls. 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 healthy controls using predefined 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 left CC, and 3) right anterior IC and left superior temporal gyrus. Healthy controls displayed greater connectivity between left anterior IC and bilateral medial frontal gyrus/anterior cingulate cortex; and left posterior IC and 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, which may play 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 FM.