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Functional gastrointestinal disorders (FGIDs) affect an extensive population and bring along high costs. Various alterations in perception of visceral stimuli have been reported in these patients, and previous research has recently demonstrated the ability of fear learning to alter perception of exteroceptive stimuli. The aim of this study was to learn more about the effect of associative fear learning on perception of visceral stimuli in general and visceral discrimination in particular. As literature on the just-noticeable difference thresholds for visceral sensations is lacking, a pilot was performed to identify variations in just-noticeable difference. Next, in the actual experiment, changes in discrimination acuity were assessed after differential interoceptive fear conditioning. We adopted a set of 2 hardly discriminable esophageal balloon stimuli as conditioned stimuli (CSs). During a conditioning phase, one of these was always followed by a noxious electrical stimulus (unconditioned stimulus (US)), while the other one was never followed by the US. A 3 alternative-forced choice ask was used to investigate how well participants discriminated between both CSs before and after conditioning. Galvanic skin responses and subjective ratings suggest no differential fear learning occurred. Taken together, the results indicate that our manipulation did not succeed and therefore the relation between fear conditioning and visceral discrimination remains unclear. Recommendations for future research addressing this topic will be given.
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Background: Chronic fatigue syndrome (CFS) remains the subject of controversy because of its unknown etiology and pathophysiology. The disease is characterized by a wide range of symptoms, most importantly extreme fatigue. Although the etiology of CFS is unknown, studies show evidence for central nervous system (CNS) and/or immune system abnormalities. Together with the common co-morbidity of gastrointestinal symptoms, recent research in CFS focuses on the putative involvement of the gut microbiota, acting through the gut-brain axis. More specifically, perturbation of the intestinal microbial community (i.e. dysbiosis) in CFS might lead to gastrointestinal discomfort, peripheral inflammation and neuroinflammation. This systematic review summarizes published microbiome studies in CFS patients to explore the hypothesis for a role of the gut microbiota in the etiology and pathophysiology of CFS. Methods: A literature search was conducted using the electronic databases PubMed, Embase, Web of Science and Google Scholar. After applying the specific search terms, all articles were screened on title and abstract. The included studies were assessed for methodological quality using the Critical Appraisal Skills Programme (CASP) checklist. Data pooling was prevented due to poor quality of and variability between the studies. Results: Nine articles were included in the analysis. All studies but one recorded significant alterations of the gut microbiota in the CFS cohort in comparison to healthy controls. However, the results appeared to be inconsistent and difficult to interpret. The main reason for these conflicting results is the poor quality of the included studies, due to the lack of statistical power, emerging from small sample sizes. Conclusion: There is insufficient evidence to confirm a link between dysbiosis and the etiology and pathophysiology of CFS. Future research should focus on proper sample size and study design, i.e. longitudinal studies, to define causality and to control for confounding factors within the study population.
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Background. Globus is the uncomfortable feeling of a lump in the throat. Although a lot of research has been done on the subject, the etiology remains unclear. Chen et al. (2009) suggested visceral hypersensitivity and aberrant symptom referral as a possible cause. Aim. To assess differences in perception thresholds and symptom location during repeated esophageal and UES balloon distension in subjects with and without globus.Methods. 44 globus patients and 25 healthy controls participated. Perception and discomfort thresholds were assessed using stepwise isobaric esophageal balloon distensions (2mmHg/30sec). The barostat balloon was located in the UES and in the esophageal body 10 cm below the UES. Both tests were repeated, with the second measurement immediately following the first. Location of perception was indicated on a body map. A mixed procedure, two-way ANOVA, was used to analyze the data. Results. Patients showed more proximal discomfort during the second esophageal distension in comparison the first distension (1.62 cm vs. 2.39 cm above the xyphoid, p=0.0030), whereas controls showed no significant changes. Patients showed lower discomfort thresholds at second distension (sensitization, from 21.41 mmHg vs. 17.19 mmHg, p<.0001) whereas controls did not show any significant changes. Combined, this indicates that the lower the discomfort thresholds, the higher patients perceive the sensation of discomfort, as confirmed by mixed regression analysis. Conclusion. Globus patients perceive the sensation evoked by repeated esophageal balloon distension significantly higher than healthy control. In addition, patients show lowered discomfort thresholds during the second compared to the first distension sequence, whereas controls show no significant changes. We can conclude that the globus patients are characterized by sensitization upon repeated esophageal distension, corresponding with increased height of symptom perception.
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The interaction between stress and fear conditioning serves as an illuminating model in the understanding of anxiety disorders. Previous work has shown that stress may change subsequent fear acquisition and extinction learning, likely through the stress hormone cortisol. However, variable effects have been described, ranging from facilitative, inhibitory, to null effects. In this article, we first performed a systematic review on the association of stress on subsequent fear acquisition and extinction learning in men. Then, we performed secondary analysis on an existing dataset comprising 133 men who underwent the Maastricht Acute Stress Test (MAST) prior to completing a fear acquisition and extinction task. We examined whether cortisol response trajectories derived from latent-class growth analysis (mild responders (n = 15), moderately-low responders (n = 46), moderately-high responders (n = 48), and hyper responders (n = 24)) could predict the rate of fear acquisition and/or extinction learning, as assessed by US expectancy ratings and skin conductance responses (SCRs). Our systematic review did not reveal a clear consensus pertaining to the association of stress on subsequent fear acquisition. For fear extinction, a negative association of stress exposure, and thus greater extinction resistance, was indicated. In our analysis, we found no significant associations between cortisol response trajectories in response to the MAST and subsequent fear acquisition. We did find an association with extinction learning as assessed by US expectancy ratings, suggesting better safety learning in participants with a hyper-responder cortisol trajectory participant. In addition, during extinction learning, higher overall SCRs were observed in these hyper-responders, indicating greater general arousal during extinction learning independent of stimulus type. These results demonstrate that cortisol responsiveness to a psychosocial stressor interferes with rate of extinction learning at the subjective level and promoted general arousal during this phase at the physiological level. As extinction learning is the theoretical model of exposure therapy, these findings could have clinical implications.
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