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Muri, Switzerland

Wong R.K.,National University of Singapore | Van Oudenhove L.,Catholic University of Leuven | Li X.,National University of Singapore | Cao Y.,National University of Singapore | And 3 more authors.
United European Gastroenterology Journal | Year: 2016

Background: The MRI scanner environment induces marked psychological effects, but specific effects on pain perception and processing are unknown and relevant to all brain imaging studies. Objectives and methods: We performed visceral and somatic quantitative sensory and pain testing and studied endogenous pain modulation by heterotopic stimulation outside and inside the functional MRI scanner in 11 healthy controls and 13 patients with irritable bowel syndrome. Results: Rectal pain intensity (VAS 0–100) during identical distension pressures increased from 39 (95% confidence interval: 35–42) outside the scanner to 53 (43–63) inside the scanner in irritable bowel syndrome, and from 42 (31–52) to 49 (39–58), respectively, in controls (ANOVA for scanner effect: p=0.006, group effect: p=0.92). The difference in rectal pain outside versus inside correlated significantly with stress (r=-0.76, p=0.006), anxiety (r=-0.68, p=0.02) and depression scores (r=-0.67, p=0.02) in controls, but not in irritable bowel syndrome patients, who a priori had significantly higher stress and anxiety scores. ANOVA analysis showed trends for effect of the scanner environment and subject group on endogenous pain modulation (p=0.09 and p=0.1, respectively), but not on somatic pain (p>0.3). Conclusion: The scanner environment significantly increased visceral, but not somatic, pain perception in irritable bowel syndrome patients and healthy controls in a protocol specifically aimed at investigating visceral pain. Psychological factors, including anxiety and stress, are the likely underlying causes, whereas classic endogenous pain modulation pathways activated by heterotopic stimulation play a lesser role. These results are highly relevant to a wide range of imaging applications and need to be taken into account in future pain research. Further controlled studies are indicated to clarify these findings. © Author(s) 2016. Source

Li X.,National University of Singapore | Kan E.M.,Combat Care Laboratory | Lu J.,Combat Care Laboratory | Cao Y.,National University of Singapore | And 4 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2013

Background Gastrointestinal (GI) symptoms are common in soldiers in combat or high-pressure operational situations and often lead to compromised performance. Underlying mechanisms are unclear, but neuroendocrine dysregulation, immune activation and increased intestinal permeability may be involved in stress-related GI dysfunction. Aim To study the effects of prolonged, intense, mixed psychological and physical stress on intestinal permeability, systemic inflammatory and stress markers in soldiers during high-intensity combat-training. Methods In 37 male army medical rapid response troops, GI symptoms, stress markers, segmental intestinal permeability using the 4-sugar test (sucrose, lactulose, mannitol and sucralose) and immune activation were assessed during the 4th week of an intense combat-training and a rest period. Results Combat-training elicited higher stress, anxiety and depression scores (all P < 0.01) as well as greater incidence and severity of GI symptoms [irritable bowel syndrome symptom severity score (IBS-SSS), P < 0.05] compared with rest. The IBS-SSS correlated with depression (r = 0.41, P < 0.01) and stress (r = 0.40, P < 0.01) ratings. Serum levels of cortisol, interleukin-6, and tumour necrosis factor-α, and segmental GI permeability increased during combat-training compared with rest (all P < 0.05). The lactulose:mannitol ratio was higher in soldiers with GI symptoms (IBS-SSS ≥75) during combat-training than those without (IBS-SSS <75) (P < 0.05). Conclusions Prolonged combat-training not only induces the expected increases in stress, anxiety and depression, but also GI symptoms, pro-inflammatory immune activation and increased intestinal permeability. Identification of subgroups of individuals at high-risk of GI compromise and of long-term deleterious effects of operational stress as well as the development of protective measures will be the focus of future studies. © 2013 Blackwell Publishing Ltd. Source

Wilder-Smith C.,Brain Gut Research Group | Rohss K.,Astrazeneca | Bokelund Singh S.,Astrazeneca | Sagar M.,Astrazeneca | Nagy P.,Astrazeneca
Alimentary Pharmacology and Therapeutics | Year: 2010

Aliment Pharmacol Ther 2010; 32: 1249-1256 Summary Background Symptoms of gastro-oesophageal reflux disease (GERD) may persist despite daily treatment with a proton pump inhibitor (PPI). Aim To compare the pharmacodynamic effect of various esomeprazole dosage and timing regimens in healthy volunteers. Methods The effect of different esomeprazole dosage regimens [20 mg once daily (od) before breakfast or dinner; 20 mg twice daily (b.d.); 40 mg od before breakfast, dinner or at bedtime; and 40 mg b.d.] on 24-h, daytime and night-time acid inhibition was evaluated in a randomized, seven-way crossover study in healthy volunteers. Each regimen was taken for 5 days. Results Over the 24-h period (day 5), esomeprazole 20 mg b.d. was associated with superior acid inhibition vs. all 20 mg and 40 mg od regimens (P < 0.05), but was less effective than esomeprazole 40 mg b.d. (P < 0.05). Dosing with esomeprazole 20 mg or 40 mg od before breakfast gave improved 24-h and daytime acid inhibition vs. the corresponding administration before dinner or at bedtime (all P < 0.05). Night-time acid inhibition was improved when esomeprazole 40 mg od was administered before dinner or at bedtime vs. before-breakfast dosing (P < 0.05). Conclusion Varying the dose and timing of esomeprazole administration may provide acid inhibition appropriate for the symptom pattern of individual patients with GERD. © 2010 Blackwell Publishing Ltd. Source

Phua L.C.,National University of Singapore | Wilder-Smith C.H.,National University of Singapore | Wilder-Smith C.H.,Brain Gut Research Group | Tan Y.M.,National University of Singapore | And 7 more authors.
Journal of Proteome Research | Year: 2015

Physical and psychological stress have been shown to modulate multiple aspects of gastrointestinal (GI) physiology, but its molecular basis remains elusive. We therefore characterized the stress-induced metabolic phenotype (metabotype) in soldiers during high-intensity combat training and correlated the metabotype with changes in GI symptoms and permeability. In a prospective, longitudinal study, urinary metabotyping was conducted on 38 male healthy soldiers during combat training and a rest period using gas chromatography-mass spectrometry. The urinary metabotype during combat training was clearly distinct from the rest period (partial least-squares discriminant analysis (PLSDA) Q2 = 0.581), confirming the presence of a unique stress-induced metabotype. Differential metabolites related to combat stress were further uncovered, including elevated pyroglutamate and fructose, and reduced gut microbial metabolites, namely, hippurate and m-hydroxyphenylacetate (p < 0.05). The extent of pyroglutamate upregulation exhibited a positive correlation with an increase in IBS-SSS in soldiers during combat training (r = 0.5, p < 0.05). Additionally, the rise in fructose levels was positively correlated with an increase in intestinal permeability (r = 0.6, p < 0.005). In summary, protracted and mixed psychological and physical combat-training stress yielded unique metabolic changes that corresponded with the incidence and severity of GI symptoms and alteration in intestinal permeability. Our study provided novel molecular insights into stress-induced GI perturbations, which could be exploited for future biomarker research or development of therapeutic strategies. © 2015 American Chemical Society. Source

Li X.,National University of Singapore | Cao Y.,National University of Singapore | Wong R.K.M.,National University of Singapore | Ho K.Y.,National University of Singapore | And 2 more authors.
Neurogastroenterology and Motility | Year: 2013

Background Visceral hypersensitivity is one of the proposed underlying mechanisms in functional dyspepsia (FD). It is not clear whether visceral hypersensitivity in FD is a manifestation of a central sensitization also encompassing somatic sensitization. Transient receptor potential vanilloid-1 (TRPV1) pathways are involved in gastric mechanosensory physiology and the TRPV1 receptor agonist, capsaicin, has been used as a chemical stimulant. Methods In this double-blind, randomized study we evaluated both visceral and somatic sensory function in 34 FD patients and 42 healthy controls using quantitative sensory testing. Visceral pain sensitivity was assessed using a validated gastric pain model with oral capsaicin capsule titration and somatic pain sensitivity was determined by foot heat and hand electric stimulation. Key Results The median capsaicin dose required to attain moderate pain was 0.5mg in FD and 1mg in controls (P=0.03). At these doses, mean pain intensities on a 0-100 visual analog scale were greater for FD than controls [56.9 (95% confidence intervals, 52.2-61.5) vs 45.1 (41.6-48.6), resp.] (P=0.005). Overall, mean somatic sensory and pain thresholds were similar in FD and control groups, but in a subgroup of FD pain hypersensitivity was seen on the hand and on the foot at different stimulation thresholds. Conclusions & Inferences A majority of patients with FD have visceral chemo-hypersensitivity involving TRPV1 pathways. A substantial subgroup also has somatic hypersensitivity as evidence of central sensitization. © 2012 Blackwell Publishing Ltd. Source

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