Mechanisms contributing to visceral hypersensitivity : focus on splanchnic afferent nerve signalling

This is the peer reviewed version of the following article: Deiteren, A., De Man, J. G., Keating, C., Jiang, W., De Schepper, H. U., Pelckmans, P. A., Francque, S. M. and De Winter, B. Y. (2015), Mechanisms contributing to visceral hypersensitivity: focus on splanchnic afferent nerve signaling. Neurogastroenterology & Motility, 27: 1709–1720, which has been published in final form at doi:10.1111/nmo.12667. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Visceral hypersensitivity is a main characteristic of functional bowel disorders and is mediated by both peripheral and central factors. We investigated whether enhanced splanchnic afferent signaling in vitro is associated with visceral hypersensitivity in vivo in an acute and postinflammatory rat model of colitis.Peer reviewedFinal Accepted Versio

Real-time risk analysis for hybrid earthquake early warning systems

Earthquake Early Warning Systems (EEWS), based on real-time prediction of ground motion or structural response measures, may play a role in reducing vulnerability and/or exposition of buildings and lifelines. In fact, recently seismologists developed efficient methods for rapid estimation of event features by means of limited information of the P-waves. Then, when an event is occurring, probabilistic distributions of magnitude and source-to-site distance are available and the prediction of the ground motion at the site, conditioned to the seismic network measures, may be performed in analogy with the Probabilistic Seismic Hazard Analysis (PSHA). Consequently the structural performance may be obtained by the Probabilistic Seismic Demand Analysis (PSDA), and used for real-time risk management purposes. However, such prediction is performed in very uncertain conditions which have to be taken into proper account to limit false and missed alarms. In the present study, real-time risk analysis for early warning purposes is discussed. The magnitude estimation is performed via the Bayesian approach, while the earthquake localization is based on the Voronoi cells. To test the procedure it was applied, by simulation, to the EEWS under development in the Campanian region (southern Italy). The results lead to the conclusion that the PSHA, conditioned to the EEWS, correctly predicts the hazard at the site and that the false/missed alarm probabilities may be controlled by set up of an appropriate decisional rule and alarm threshold

Effect of Meal Ingestion on Ileocolonic and Colonic Transit in Health and Irritable Bowel Syndrome

Background: Postprandial symptoms in irritable bowel syndrome (IBS) have been associated with increased bowel contractility. Aim: To compare ileocolonic and colonic responses to feeding in health and IBS. Methods: We prospectively analyzed data from separate research trials in 122 IBS patients and 41 healthy volunteers. Ileocolonic transit (ICT) was evaluated before (colonic filling [CF]3h) and immediately after (CF4h) a standard lunch at 3 h 45 min, and 2 h thereafter. The colonic geometric center (GC) was calculated 2 h (GC6h) after lunch ingested at 4 h (GC4h) and directly after (GC8h) a standard dinner ingested at 7 h 45 min. Results: ICT immediately after eating was higher in IBS diarrhea predominant (IBS-D) patients than in the healthy cohort (23.1 ± 2.4 vs. 17.5 ± 2.8%, P = 0.059). ICT 2 h after lunch was similar between groups (P = 0.55). There was significant overall group differences in colonic transit 2 h post-lunch (P = 0.045), particularly in the IBS constipation predominant (IBS-C; GC6-GC4, Δ0.29 ± 0.08) patients versus healthy volunteers (Δ0.56 ± 0.12 GC units). Conclusions: After feeding, ICT is increased in IBS-D, whereas colonic transit is blunted in IBS-C

The effect of chemically induced colitis, psychological stress and their combination on visceral pain in female Wistar rats

Visceral sensitivity is of pathophysiological importance in abdominal pain disorders and can be modulated by inflammation and stress. However, it is unclear whether inflammation and stress alter visceral perception independently of each other or in conjunction through neuroendocrine interactions. Therefore, we compared the short- and long-term effects of experimental colitis and water avoidance stress (WAS), alone or in combination, on visceral sensitivity in female Wistar rats. Colitis was induced by trinitrobenzene sulfonic acid (TNBS) and colonoscopically confirmed. During WAS, rats were placed on a platform surrounded by water for 1 h. Visceral sensitivity was assessed by quantifying the visceromotor responses (VMRs) to colorectal distension. Activation of the hypothalamic-pituitary-adrenal axis was determined by measuring serum corticosterone in a separate protocol. TNBS instillation resulted in overt colitis, associated with significant visceral hypersensitivity during the acute inflammatory phase (3 days post-TNBS; n = 8/group); after colitis had subsided (28 days post-TNBS), hypersensitivity was resolved (n = 4-8/group). Single WAS was associated with increased VMRs of a magnitude comparable to acute TNBS-induced hypersensitivity (n = 8/group). However, after repetitive WAS no significant hypersensitivity was present (n = 8/group). No additive effect of colitis and stress was seen on visceral pain perception (n = 6-8/group). Corticosterone levels were only increased in acute TNBS-colitis, acute WAS and their combination. To conclude, both colitis and stress successfully induced short-term visceral hypersensitivity and activated the hypothalamic-pituitary-adrenal axis, but long-term effects were absent. In addition, our current findings do not support an additive effect of colitis and stress on visceral sensitivity in female Wistar rats.Annemie Deiteren, Wim Vermeulen, Tom G. Moreels, Paul A. Pelckmans, Joris G. De Man, and Benedicte Y. De Winte

Histamine H4 and H1 receptors contribute to postinflammatory visceral hypersensitivity

OBJECTIVES: Substantial evidence implicates mast cells and their main constituent histamine in the pathogenesis of visceral hypersensitivity. We explored the specific contribution of histamine H4 (H4R) and H1 (H1R) receptors to visceral hypersensitivity in a postinflammatory rat model. DESIGN: Trinitrobenzenesulfonic acid (TNBS)-colitis was monitored individually by colonoscopy: first on day 3 to confirm the presence of colitis and then every 4 days, starting from day 10, to monitor convalescence and determine the exact timepoint of endoscopic healing in each rat. Experiments were performed 3 days after endoscopic resolution of colitis. Visceral sensitivity was assessed by quantifying visceromotor responses (VMRs) to colorectal distension. Colonic mast cell numbers, histamine release and H4R and H1R mRNA expression were quantified. JNJ7777120 (H4R antagonist) and/or levocetirizine (H1R antagonist) were administered 30 min prior to VMR assessment or histamine release assay. RESULTS: Postcolitis rats displayed a higher number of colonic mast cells, excessive histamine release and significantly enhanced VMRs. Heightened VMRs were dose-dependently reduced by JNJ7777120 and levocetirizine; combined administration of JNJ7777120 and levocetirizine potentiated the antinociceptive effect. In the colon, both H4R and H1R mRNA were present; in the dorsal root ganglia, only H1R mRNA was found. Only colonic H4R mRNA expression was increased in postcolitis rats. Excessive histamine release in postcolitis rats was attenuated by the highest dose of JNJ7777120. CONCLUSIONS: H4R and H1R antagonists dose-dependently reduce and even normalise postinflammatory visceral hypersensitivity via different underlying mechanisms but with a synergistic effect. Both receptor subtypes represent promising targets for the treatment of postinflammatory visceral hypersensitivity.Annemie Deiteren, Joris G De Man, Nathalie E Ruyssers, Tom G Moreels, Paul A Pelckmans, Benedicte Y De Winte