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Background: Opioids inhibit motility and secretion of the gut and have been used for antidiarrheal treatment for centuries. However, the underlying mechanisms of opium tincture are not evident., Aim: To investigate the effects of opium tincture on gastrointestinal motility, intestinal volumes, and water content of different gut segments assessed by magnetic resonance imaging (MRI)., Methods: Twenty healthy volunteers were included in a randomized, placebo-controlled, crossover study of 9 days of treatment with 30 drops of opium tincture per day. MRI was performed on day 1 (before treatment) and day 9 (during treatment). Measurements included assessments of gastric volume, gastric emptying, gastric motility, small bowel volume, small bowel water content, small bowel motility, colon volume, colon water content, and whole gut transit., Key Results: Opium tincture delayed gastric emptying by a mean difference of 5.6 min [95% CI: 1.8-9.4], p = 0.004, and increased postprandial gastric meal volume (17-21%, p = 0.02). Small bowel endpoints did not change. Opium tincture delayed whole gut transit time (p = 0.027) and increased ascending colon volume by 59 mL [95% CI: 15-103], p = 0.004, and transverse colon volume by 48 mL [95% CI: 4-92], p = 0.027. T1-relaxation time of the descending colon chyme was decreased during opium treatment, indicating dryer feces (difference: -173 ms [95% CI: -336 -11], p = 0.03)., Conclusion and Inferences: Opium tincture induced changes in the stomach and colon in healthy volunteers. An improved understanding of how opioids affect gut functions may lead to a better understanding and optimized management of diarrhea., (© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: Several magnetic resonance imaging (MRI) protocols have been used to assess gastric emptying (GE) with MRI. This systematic review summarizes the current literature on the topic. The aim was to provide an overview of the available imaging protocols and underline the items that appear most agreed upon and those that deserve further investigation., Methods: According to PRISMA guidelines, two independent reviewers conducted a systematic literature search with a pre-specified strategy in different databases. Peer-reviewed articles that utilized MRI techniques to assess GE in healthy volunteers (HVs) were included. The quality and the outcomes of the studies were reported and analyzed., Key Results: The literature search yielded 30 studies (531 HVs, weighted mean age 27.4, weighted mean body mass index 23.0 kg/m 2 ), T2-weighted sequences, balanced turbo field echo, and balanced gradient echo were evenly utilized, with volunteers in the supine position (74% of the studies). After overnight fasting, both liquid (56%) and mixed (44%) meals were equally utilized. Segmentation of the volumes was predominantly performed manually (63%) with a reported mean T50 ranging from 7 to 330 min., Conclusions & Inferences: As observed in this systematic review, MRI is a flexible tool for assessing GE. Different protocols were analyzed, showing an equal capacity to assess the GE. However, many items in these protocols still require further investigation to obtain a common standard and increase this assessment quality., (© 2022 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: Functional constipation (FC) and irritable bowel syndrome constipation type (IBS-C) share many similarities, and it remains unknown whether they are distinct entities or part of the same spectrum of disease. Magnetic resonance imaging (MRI) allows quantification of intraluminal fecal volume. We hypothesized that colonic volumes of patients with FC would be larger than those of patients with IBS-C, and that both patient groups would have larger colonic volumes than healthy controls (HC)., Methods: Based on validated questionnaires, three groups of participants were classified into FC (n = 13), IBS-C (n = 10), and HC (n = 19). The colonic volume of each subject was determined by MRI. Stool consistency was described by the Bristol stool scale and colonic transit times were assessed with radiopaque makers., Key Results: Overall, total colonic volumes were different in the three groups, HC (median 629 ml, interquartile range (IQR)(562-868)), FC (864 ml, IQR(742-940)), and IBS-C (520 ml IQR(489-593)) (p = 0.001). Patients with IBS-C had lower colonic volumes than patients with FC (p = 0.001) and HC (p = 0.019), but there was no difference between FC and HC (p = 0.10). Stool consistency was similar in the two patient groups, but patients with FC had longer colonic transit time than those with IBS-C (117.6 h versus 43.2 h, p = 0.019)., Conclusion: Patients with IBS-C have lower total colonic volumes and shorter colonic transit times than patients with FC. Future studies are needed to confirm that colonic volume allows objective distinction between the two conditions., (© 2022 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: Tapentadol is a combined opioid agonist and norepinephrine reuptake inhibitor with fewer gastrointestinal side effects at equianalgesic doses compared with classical strong opioids. Previous studies on tapentadol have included multi-morbid patients in whom confounders exclude detailed assessment of the mechanistic effects and strict comparison with other opioids or placebo. This study aimed at investigating the effects of tapentadol and oxycodone on gastrointestinal motility and gastrointestinal side effects., Methods: 21 healthy males participated in a randomized, double-blind, placebo-controlled, crossover study. Tapentadol (50 mg twice daily), oxycodone (10 mg twice daily), or placebo tablets were administered for 14 days. Segmental gastrointestinal transit times and colonic motility parameters were measured with electromagnetic capsules. Gastrointestinal side effects were assessed using questionnaires., Key Results: During dosing with tapentadol, gastrointestinal side effects and motility parameters were on placebo level. Compared with tapentadol, oxycodone increased whole gut transit time by 17.9 hours (p = .015) and rectosigmoid transit time by 6.5 hours (p = .005). Compared with tapentadol, oxycodone also reduced long, fast antegrade colonic movements (p = .001). In comparison with placebo, oxycodone prolonged whole gut transit time by 31.6 hours, (p < .001). Moreover, less long, fast antegrade colonic movements (p = .002) were observed during oxycodone. For oxycodone only, slow colonic movements were associated with gastrointestinal side effects., Conclusions & Inferences: In this mechanistic study, tapentadol caused significantly less colonic dysmotility and gastrointestinal side effects as compared with oxycodone in equianalgesic doses., (© 2021 John Wiley & Sons Ltd.)

Background: Abnormal central nervous system processing of visceral sensation may be a part of the pathogenesis behind idiopathic fecal incontinence (IFI). Our aim was to characterize brain differences in patients with IFI and healthy controls by means of structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI)., Methods: In 21 female patients with IFI and 15 female healthy controls, whole-brain structural differences in gray matter volume (GMV), cortical thickness, and white matter tracts fractional anisotropy (FA) were quantified. For this purpose, we used voxel-based morphometry, surface based morphometry and tract-based spatial statistic, respectively. Furthermore, associations between structural brain characteristics and latencies of rectal sensory evoked electroencephalography potentials were determined., Key Results: Compared to healthy controls, IFI patients had significantly reduced FA values, reflecting reduced white matter tract integrity, in the left hemisphere superior longitudinal fasciculus (SLF), posterior thalamic radiation, and middle frontal gyrus (MFG), all P<.05. No differences were observed in GMV or in cortical thickness. The reduced FA values in the SLF and MFG were correlated with prolonged latencies of cortical potentials evoked by rectal stimuli (all P<.05)., Conclusions & Inferences: This explorative study suggests that IFI patients have no macrostructural brain changes, but exhibit microstructural changes in white matter tracts relevant for sensory processing. The clinical relevance of this finding is supported by its correlations with prolonged latencies of cortical potentials evoked by rectal stimulation. This supports the theories of central nervous system changes as part of the pathogenesis in IFI patients., (© 2017 John Wiley & Sons Ltd.)

Background: The parasympathetic nervous system, whose main neural substrate is the vagus nerve, exerts a fundamental antinociceptive role and influences gastrointestinal sensori-motor function. Our research question was to whether combined electrical and physiological modulation of vagal tone, using transcutaneous electrical vagal nerve stimulation (t-VNS) and deep slow breathing (DSB) respectively, could increase musculoskeletal pain thresholds and enhance gastroduodenal motility in healthy subjects., Methods: Eighteen healthy subjects were randomized to a subject-blinded, sham-controlled, cross-over study with an active protocol including stimulation of auricular branch of the vagus nerve, and breathing at full inspiratory capacity and forced full expiration. Recording of cardiac derived parameters including cardiac vagal tone, moderate pain thresholds to muscle, and bone pressure algometry, conditioned pain modulation using a cold pressor test and a liquid meal ultrasonographic gastroduodenal motility test were performed., Key Results: Cardiac vagal tone increased during active treatment with t-VNS and DSB compared to sham (p = 0.009). In comparison to sham, thresholds to bone pain increased (p = 0.001), frequency of antral contractions increased (p = 0.004) and gastroduodenal motility index increased (p = 0.016) with active treatment. However, no effect on muscle pain thresholds and conditioned pain modulation was seen., Conclusions & Inferences: This experimental study suggests that this noninvasive approach with combined electrical and physiological modulation of vagal tone enhances gastroduodenal motility and reduces somatic pain sensitivity. These findings warrant further investigation in patients with disorders characterized with chronic pain and gastrointestinal dysmotility such as functional dyspepsia and irritable bowel syndrome., (© 2016 John Wiley & Sons Ltd.)

Background: Segmental distribution of colorectal volume is relevant in a number of diseases, but clinical and experimental use demands robust reliability and validity. Using a novel semi-automatic magnetic resonance imaging-based technique, the aims of this study were to describe: (i) inter-individual and intra-individual variability of segmental colorectal volumes between two observations in healthy subjects and (ii) the change in segmental colorectal volume distribution before and after defecation., Methods: The inter-individual and intra-individual variability of four colorectal volumes (cecum/ascending colon, transverse, descending, and rectosigmoid colon) between two observations (separated by 52 ± 10) days was assessed in 25 healthy males and the effect of defecation on segmental colorectal volumes was studied in another seven healthy males., Key Results: No significant differences between the two observations were detected for any segments (All p > 0.05). Inter-individual variability varied across segments from low correlation in cecum/ascending colon (intra-class correlation coefficient [ICC] = 0.44) to moderate correlation in the descending colon (ICC = 0.61) and high correlation in the transverse (ICC = 0.78), rectosigmoid (ICC = 0.82), and total volume (ICC = 0.85). Overall intra-individual variability was low (coefficient of variance = 9%). After defecation the volume of the rectosigmoid decreased by 44% (p = 0.003). The change in rectosigmoid volume was associated with the true fecal volume (p = 0.02)., Conclusions & Inferences: Imaging of segmental colorectal volume, morphology, and fecal accumulation is advantageous to conventional methods in its low variability, high spatial resolution, and its absence of contrast-enhancing agents and irradiation. Hence, the method is suitable for future clinical and interventional studies and for characterization of defecation physiology., (© 2015 John Wiley & Sons Ltd.)

Background: Gastrointestinal (GI) symptoms, such as nausea, vomiting, bloating, postprandial fullness, and abdominal pain, are frequent in patients with diabetes mellitus (DM). The pathogenesis is complex and multi-factorial. To determine easy accessible and valid biomarkers for disordered GI function in DM patients, we aimed to study esophageal mechanical parameters and their relation to symptoms typically arising from the digestive tract., Methods: Seventeen patients with longstanding DM and GI symptoms and 13 healthy controls were studied using ultrasound monitored esophageal distension. The sensory response was recorded and their symptoms registered. Biomechanical parameters, such as compliance and stiffness were computed from luminal diameters during distension based on the ultrasound images and from pressure data. Biomechanical and sensory parameters were correlated with the clinical data., Key Results: Diabetes patients had reduced esophageal sensitivity compared with controls (P = 0.046). The esophageal compliance was reduced (P = 0.004) and the esophageal stiffness was increased (P = 0.004) in the diabetes patients. Among patients, both postprandial fullness/early satiety and bloating correlated negatively to the esophageal compliance parameters (all P < 0.05)., Conclusions & Inferences: Patients with long-standing DM and GI symptoms had reduced esophageal sensitivity together with reduced compliance and increased stiffness, which were correlated to the patients' GI symptoms. Biomechanical parameters obtained during distension may serve as biomarker for similar pathophysiologic effects of diabetes in the stomach and small bowel. They may contribute to our understanding of the pathophysiology underlying GI dysfunction and symptoms in patients with longstanding DM., (© 2012 Blackwell Publishing Ltd.)

Evaluation of rectal and rectosigmoid sensation is important in basic, clinical and pharmacological studies. New methods to evoke and assess multimodal (electrical, thermal and mechanical) experimental pain of the upper gut activate distinct pathways and mimics clinical pain. The aims of the current study were to characterize the sensory response and reproducibility to multimodal stimulation of rectum and the rectosigmoid. A multimodal rectal probe was developed. Mucosal electrostimulation was delivered at the recto-sigmoid junction. In Rectum, impedance planimetry was used for measurement of cross-sectional area (CSA) during distension. Circulation of water within the bag at either 4 or 60 degrees C was applied for thermal stimulation. The method was tested in 12 healthy volunteers (six men mean age 32 years) on two subsequent days. Mechanical and sensory responses and referred pain areas were assessed. Stimulation with electrical, thermal and mechanical modalities resulted in different sensory perceptions. The relationship between stimulus intensity and sensory response was linear for all modalities. Sensory response to different modalities did not differ between investigation days (all P-values > 0.1). Approximately 75% of subjects felt referred pain in distinct skin locations. Between-days reproducibility was good for all modalities [intra-class correlation (ICC) > or = 0.6]. At sensory threshold, CSA showed best reproducibility (ICC > or = 0.9). At pain detection threshold stretch ratio, CSA and electrostimulation showed best reproducibility (ICC = 1.0; 0.9; 0.9). The present model was easily implemented, robust and showed good reproducibility. It can be used to study pathophysiology or pharmacological interventions in healthy controls and in patients with diseases involving the distal hindgut.

The aim of this study was to use magnetic resonance imaging (MRI) to evaluate the three-dimensional geometry and mechanosensory properties of the sigmoid colon. The sigmoid colon was stepwise distended by a water-filled bag in eight subjects. Simultaneous MRI, bag pressure recording and sensory assessment were performed before and after smooth muscle relaxation with butylscopolamine. The surface distributions of principal curvature radii, wall thickness, tension, stress and circumferential strain were calculated. The geometry of the distended sigmoid colon was complex and the spatial distributions of the biomechanical parameters were non-homogeneous. The circumferential length, strain, pressure and wall stress increased as a function of bag volume (all P < 0.001). In response to butylscopolamine, the pressure and wall stress were reduced (P < 0.05) and the stress-strain curves were shifted to the right. The sensory response was a linear function of the biomechanical parameters (all P < 0.001) and decreased in response to butylscopolamine as a function of volume (P = 0.02). The stimulus-response data indicate that the mechanosensitive afferents are affected by smooth muscle tone. The present study provides a method for characterizing the complex geometry and mechanical properties of the sigmoid colon, including the role of smooth muscle tone. This may be valuable in understanding of the biomechanical and mechanosensory functions in colonic diseases.

Evaluation of the distribution of stresses and strains in relation to distension-induced sensation in the human oesophagus is valuable for understanding oesophageal biomechanics and mechano-sensation. In 12 healthy volunteers a specially designed oesophageal bag containing an endoscopic ultrasound probe was inflated to the moderate pain level. Ultrasound images, bag pressure and perceived sensation were recorded before and after pharmacological relaxation of the smooth muscle with butylscopolamine. The oesophagus was assumed to be circular and thick-walled. Distension induced a tensile circumferential stretch, radial compression and longitudinal shortening. Both circumferential strain and stress were highest at the mucosal surface and decreased throughout the wall. The stiffness increased throughout the wall and was highest at the outer surface (P < 0.001). The decrease in stiffness in response to butylscopolamine was non-significant. The infused volume (P = 0.012) and circumferential stress (P < 0.001) were most closely associated with the distension-induced sensation (adjusted R2 = 0.88). The perceived sensation was highly individual but was unaffected by butylscopolamine (P > 0.08). The present study provides a method for computation of the stress-strain distribution throughout the wall and the mechano-sensory interaction in the human oesophagus. In the future, this may be useful for understanding of mechanoreceptor responses and generation of symptoms in visceral organs in health and in disease.

A method to evaluate the three-dimensional (3-D) geometry of the human gastrointestinal wall may be valuable for understanding tissue biomechanics, mechano-sensation and function. In this paper we present a magnetic resonance imaging (MRI) based method to determine rectal geometry and validation of data obtained in three volunteers. A specially designed rectal bag was filled in a stepwise manner while MRI and bag pressure were recorded. 3-D models of curvatures, radii of curvature, tension and stress were generated and the circumferential and longitudinal strains were calculated. The computed bag volumes corresponded to the infused volumes. A pronounced bag elongation and decrease in wall thickness was observed during the bag filling. The spatial distributions of the biomechanical parameters were distinctly different between individuals and non-homogeneous throughout the rectal wall due to its complex geometry. The average tension and stress increased as a function of infused volume and circumferential strain. The present study provides a method for characterizing the complex in vivo 3-D geometry of the human rectum. The non-homogenous spatial curvature distribution suggests that simple estimates of tension based on pressure and volume do not reflect the true 3-D biomechanical properties of the rectum.

Knowledge of the competence of the oesophago-gastric junction (OGJ) is fundamental to the understanding of gastro-oesophageal reflux disease (GORD), a disorder with a high incidence among the general population. A catheter with a bag 9.5 cms long mounted towards the distal end was swallowed by three volunteers. Using manometry readings and the point of respiratory inversion as a guide the probe was placed in the OGJ. The bag was distended with saline at a fixed rate volume before and after the administration of butylscopolamine to block cholinergic-mediated contractile smooth muscle activity. Using impedance planimetry three cross-sectional areas (CSA) measurements were made between three pairs of electrodes with 4 mm between each electrode on the catheter placed inside the ballon. Using the law of Laplace, CSA and pressure data could be calculated to give wall tension. Tension rose in all volunteers as the radius increased and it was higher towards the proximal end of the OGJ indicating that this measurement can be used to show the distensibility of the OGJ at different degrees of opening. This technique could be useful in identifying changes in the competence of the lower oesophageal sphincter in some patients with GORD.