Pain is a highly complex and individualized experience with biopsychosocial components. Neuroimaging research has shown evidence of the involvement of the central nervous system in the development ...and maintenance of chronic pain conditions, including urological chronic pelvic pain syndrome (UCPPS). Furthermore, a history of early adverse life events (EALs) has been shown to adversely impact symptoms throughout childhood and into adulthood. However, to date, the role of EAL's in the central processes of chronic pain have not been adequately investigated. We studied 85 patients (56 females) with UCPPS along with 86 healthy controls (HCs) who had resting-state magnetic resonance imaging scans (59 females), and data on EALs as a part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Study. We used graph theory methods in order to investigate the impact of EALs on measures of centrality, which characterize information flow, communication, influence, and integration in a priori selected regions of interest. Patients with UCPPS exhibited lower centrality in the right anterior insula compared to HCs, a key node in the salience network. Males with UCPPS exhibited lower centrality in the right anterior insula compared the HC males. Females with UCPPS exhibited greater centrality in the right caudate nucleus and left angular gyrus compared to HC females. Males with UCPPS exhibited lower centrality in the left posterior cingulate, angular gyrus, middle temporal gyrus, and superior temporal sulcus, but greater centrality in the precuneus and anterior mid-cingulate cortex (aMCC) compared to females with UCPPS. Higher reports of EALs was associated with greater centrality in the left precuneus and left aMCC in females with UCPPS. This study provides evidence for disease and sex-related alterations in the default mode, salience, and basal ganglia networks in patients with UCPPS, which are moderated by EALs, and associated with clinical symptoms and quality of life (QoL).
Studies have suggested chronic pain syndromes are associated with neural reorganization in specific regions associated with perception, processing, and integration of pain. Urological chronic pelvic ...pain syndrome (UCPPS) represents a collection of pain syndromes characterized by pelvic pain, namely Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) and Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS), that are both poorly understood in their pathophysiology, and treated ineffectively. We hypothesized patients with UCPPS may have microstructural differences in the brain compared with healthy control subjects (HCs), as well as patients with irritable bowel syndrome (IBS), a common gastrointestinal pain disorder. In the current study we performed population-based voxel-wise DTI and super-resolution track density imaging (TDI) in a large, two-center sample of phenotyped patients from the multicenter cohort with UCPPS (N = 45), IBS (N = 39), and HCs (N = 56) as part of the MAPP Research Network. Compared with HCs, UCPPS patients had lower fractional anisotropy (FA), lower generalized anisotropy (GA), lower track density, and higher mean diffusivity (MD) in brain regions commonly associated with perception and integration of pain information. Results also showed significant differences in specific anatomical regions in UCPPS patients when compared with IBS patients, consistent with microstructural alterations specific to UCPPS. While IBS patients showed clear sex related differences in FA, MD, GA, and track density consistent with previous reports, few such differences were observed in UCPPS patients. Heat maps illustrating the correlation between specific regions of interest and various pain and urinary symptom scores showed clustering of significant associations along the cortico-basal ganglia-thalamic-cortical loop associated with pain integration, modulation, and perception. Together, results suggest patients with UCPPS have extensive microstructural differences within the brain, many specific to syndrome UCPPS versus IBS, that appear to be localized to regions associated with perception and integration of sensory information and pain modulation, and seem to be a consequence of longstanding pain.
With limited efficacy of medications for symptom relief, non-medication treatments may play an important role in the treatment of irritable bowel syndrome (IBS), the most common functional ...gastrointestinal (GI) disorder. This study aimed to evaluate the efficacy of two self-regulation strategies for symptom relief and mood management in IBS patients. Thirty-five adult participants meeting ROME III criteria for IBS were enrolled, 27 of the 35 participants (77%) completed treatment and pre- and post-treatment visits (89% women, 11% men; M (SD) age = 36 (13)), and 20 of the 27 (74%) completed a 6-month follow-up. Participants were randomly assigned to 16 biweekly group sessions of Iyengar yoga or a walking program. Results indicated a significant group by time interaction on negative affect with the walking treatment showing improvement from pre- to post-treatment when compared to yoga (p < .05). There was no significant group by time effect on IBS severity. Exploratory analyses of secondary outcomes examined change separately for each treatment condition. From pre- to post-treatment, yoga showed significant decreases in IBS severity measures (p < .05), visceral sensitivity (p < .05), and severity of somatic symptoms (p < .05). Walking showed significant decreases in overall GI symptoms (p < .05), negative affect (p < .05), and state anxiety (p < .05). At 6-month follow-up, overall GI symptoms for walking continued to significantly decline, while for yoga, GI symptoms rebounded toward baseline levels (p < .05). When asked about self-regulated home practice at 6 months, significantly more participants in walking than in yoga practiced at least weekly (p < .05). In sum, results suggest that yoga and walking as movement-based self-regulatory behavioral treatments have some differential effects but are both beneficial for IBS patients, though maintenance of a self-regulated walking program may be more feasible and therefore more effective long term.
Recent evidence points to a possible overlap in the neural systems underlying the distressing experience that accompanies physical pain and social rejection (
Eisenberger et al., 2003). The present ...study tested two hypotheses that stem from this suggested overlap, namely: (1) that baseline sensitivity to physical pain will predict sensitivity to social rejection and (2) that experiences that heighten social distress will heighten sensitivity to physical pain as well. In the current study, participants’ baseline cutaneous heat pain unpleasantness thresholds were assessed prior to the completion of a task that manipulated feelings of social distress. During this task, participants played a virtual ball-tossing game, allegedly with two other individuals, in which they were either continuously included (social inclusion condition) or they were left out of the game by either never being included or by being overtly excluded (social rejection conditions). At the end of the game, three pain stimuli were delivered and participants rated the unpleasantness of each. Results indicated that greater baseline sensitivity to pain (lower pain unpleasantness thresholds) was associated with greater self-reported social distress in response to the social rejection conditions. Additionally, for those in the social rejection conditions, greater reports of social distress were associated with greater reports of pain unpleasantness to the thermal stimuli delivered at the end of the game. These results provide additional support for the hypothesis that pain distress and social distress share neurocognitive substrates. Implications for clinical populations are discussed.
The Visceral Sensitivity Index (VSI) was developed as the first instrument to assess gastrointestinal-specific anxiety, the cognitive, affective, and behavioral response to fear of gastrointestinal ...sensations, symptoms, and the context in which these visceral sensations and symptoms occur. The purpose of the current study was to a) replicate the previously reported psychometric properties of the VSI, b) assess the known-groups and concurrent validity of the instrument, and c) test conceptual hypotheses regarding gastrointestinal-specific anxiety in comparison to other general measures of psychological distress as a crucial mechanism (mediator/moderator) underlying irritable bowel syndrome diagnosis and its symptoms.
Two undergraduate student samples (n > 500) were administered the VSI along with measures assessing presence of lower gastrointestinal symptoms, nongastrointestinal pain, health-service utilization, anxiety, depression, vitality, neuroticism, and anxiety sensitivity. Path analyses tested the hypothesis that gastrointestinal-specific anxiety mediates the relationship between affective variables and irritable bowel syndrome diagnosis and symptoms. A 'known-groups' validity approach elucidated the relevance of gastrointestinal-specific anxiety across a spectrum of irritable bowel syndrome patients.
Good concurrent, divergent and discriminant validity was demonstrated. Logistic regression revealed that gastrointestinal-specific anxiety is the key explanatory variable of irritable bowel syndrome diagnostic status. Path analysis demonstrated that gastrointestinal-specific anxiety mediates the relationship between general psychological distress measures and gastrointestinal symptom severity. The VSI was related to gastrointestinal, but not nongastrointestinal, symptom severity.
Overall, the VSI demonstrated excellent psychometric properties providing further support for its use in mechanistic studies of the role of anxiety in irritable bowel syndrome presentation.
BACKGROUND:Irritable bowel syndrome (IBS) is a stress-sensitive disorder of brain-gut interactions associated with a higher prevalence of early adverse life events (EALs). However, it is incompletely ...understood how trauma severity or disclosure influence the risk of developing IBS or symptom severity.
AIMS:To determine whether (1) IBS patients report a greater number of EALs compared with healthy controls; (2) trauma severity and first age of EAL increase the odds of IBS; (3) confiding in others reduces the odds of IBS; (4) the number, trauma severity, and first age of EAL are associated with symptom severity; (5) sex differences exist.
METHODS:In total, 197 IBS patients (72% women, mean age=30.28 y) and 165 healthy controls (59% women, mean age=30.77 y) completed the Childhood Traumatic Events Scale, measuring severity of EALs and degree of confiding in others. Regression analyses were used to predict IBS status from EALs and association between gastrointestinal symptoms and EALs.
RESULTS:A greater number of EALs odds ratio (OR)=1.36, 95% confidence interval (CI), 1.14-1.62; P<0.001 and higher perceived trauma severity (OR=1.13, 95% CI, 1.08-1.19; P<0.001) were associated with increased odds of IBS. Confiding in others decreased the odds of having IBS (OR=0.83, 95% CI, 0.72-0.96; P=0.012). The first age of EAL was not predictive of IBS. No sex differences were found.
CONCLUSIONS:Assessing the traumatic severity of EALs and amount of confiding in others is important as they can affect the risk of having IBS. Our findings emphasize early intervention to improve health outcomes in individuals with EALs.
The current study involving patients with chronic visceral pain associated with irritable bowel syndrome demonstrates microstructural differences in the brain compared with healthy control subjects, ...indicative of long-term neural reorganization of chronic pain pathways and regions associated with sensory integration.
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by recurring abdominal pain associated with alterations in bowel habits. We hypothesized that patients with chronic visceral pain associated with IBS may have microstructural differences in the brain compared with healthy control subjects (HCs), indicative of long-term neural reorganization of chronic pain pathways and regions associated with sensory integration. In the current study we performed population-based voxel-wise diffusion tensor imaging (DTI) comparisons and probabilistic tractography in a large sample of phenotyped patients with IBS (n=33) and in HCs (n=93). Patients had lower fractional anisotropy (FA) in thalamic regions, the basal ganglia (BG) and sensory/motor association/integration regions as well as higher FA in frontal lobe regions and the corpus callosum. In addition, patients had reduced mean diffusivity (MD) within the globus pallidus (GP) and higher MD in the thalamus, internal capsule, and coronal radiata projecting to sensory/motor regions, suggestive of differential changes in axon/dendritic density in these regions. Sex differences in FA and MD were also observed in the patients but not in HCs. Probabilistic tractography in patients confirmed a higher degree of connectivity between the thalamus and prefrontal cortex, as well as between the medial dorsal thalamic nuclei and anterior cingulate cortex, and a lower degree of connectivity between the GP and thalamus. Together, these results support the hypothesis that patients with chronically recurring visceral pain from IBS have long-term microstructural changes within the brain, particularly in regions associated with integration of sensory information and corticothalamic modulation.
There is growing recognition that bidirectional signaling between the digestive tract and the brain contributes to irritable bowel syndrome (IBS). We recently showed in a large randomized controlled ...trial that cognitive behavioral therapy (CBT) reduces IBS symptom severity. This study investigated whether baseline brain and gut microbiome parameters predict CBT response and whether response is associated with changes in the brain-gut-microbiome (BGM) axis.
Eighty-four Rome III-diagnosed IBS patients receiving CBT were drawn from the Irritable Bowel Syndrome Outcome Study (IBSOS; ClinicalTrials.gov NCT00738920) for multimodal brain imaging and psychological assessments at baseline and after study completion. Fecal samples were collected at baseline and post-treatment from 34 CBT recipients for 16S rRNA gene sequencing, untargeted metabolomics, and measurement of short-chain fatty acids. Clinical measures, brain functional connectivity and microstructure, and microbiome features associated with CBT response were identified by multivariate linear and negative binomial models.
At baseline, CBT responders had increased fecal serotonin levels, and increased Clostridiales and decreased Bacteroides compared to non-responders. A random forests classifier containing 11 microbial genera predicted CBT response with high accuracy (AUROC 0.96). Following treatment, CBT responders demonstrated reduced functional connectivity in regions of the sensorimotor, brainstem, salience, and default mode networks and changes in white matter in the basal ganglia and other structures. Brain changes correlated with microbiome shifts including Bacteroides expansion in responders.
Pre-treatment intestinal microbiota and serotonin levels were associated with CBT response, suggesting that peripheral signals from the microbiota can modulate central processes affected by CBT that generate abdominal symptoms in IBS. CBT response is characterized by co-correlated shifts in brain networks and gut microbiome that may reflect top-down effects of the brain on the microbiome during CBT. Video abstract.
Background & Aims Several studies have examined structural brain changes associated with chronic pain syndromes, including irritable bowel syndrome (IBS), but study sample sizes have been small and ...heterogeneous. Methods We used magnetic resonance imaging–based techniques, voxel-based morphometry, and cortical thickness analysis to examine brain anatomical differences in a relatively large, tightly screened sample of IBS patients (n = 55); we compared data with that from healthy persons (controls; n = 48). Results IBS was associated with decreased gray matter density (GMD) in widespread areas of the brain, including medial prefrontal and ventrolateral prefrontal cortex, posterior parietal cortex, ventral striatum, and thalamus. Compared with controls, we observed increased GMD in patients with IBS in the pregenual anterior cingulate cortex and the orbitofrontal cortex, as well as trends in the posterior insula/secondary somatosensory cortex, (para)hippocampus, and left dorsolateral prefrontal cortex. In accounting for anxiety and depression, we found that several of the regions involved in affective processing no longer differed between patients with IBS and controls, whereas the differences in prefrontal and posterior parietal cortices remained. The areas of decreased GMD associated with IBS were largely consistent across clinical subgroups, based on predominant bowel habit and pain predominance of symptoms. No overall or regional differences were observed in cortical thickness between patients with IBS and controls. Conclusions Changes in density of gray matter among regions involved in cognitive/evaluative functions are specifically observed in patients with IBS, whereas changes in other areas of the brain can be explained by levels of anxiety and depression.
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