Regional Cerebral Blood Flow During Gastric Balloon Distention in Functional Dyspepsia
2007; Elsevier BV; Volume: 132; Issue: 5 Linguagem: Inglês
10.1053/j.gastro.2007.03.037
ISSN1528-0012
AutoresJoris Vandenberghe, Patrick Dupont, Lukas Van Oudenhove, Guy Bormans, Koen Demyttenaere, Benjamin Fischler, Brecht Geeraerts, Jozef Janssens, Jan Tack,
Tópico(s)Gastroesophageal reflux and treatments
ResumoBackground & Aims: Hypersensitivity to proximal gastric distention as a result of abnormal central nervous system processing of visceral stimuli is a possible pathophysiologic mechanism in functional dyspepsia (FD). Increasing evidence suggests involvement of both lateral and medial pain systems in normal visceral sensitivity and aberrant brain activation patterns in visceral hypersensitivity. We hypothesized that there is involvement of aberrant brain activation in FD with hypersensitivity to gastric distention. Our aim was to investigate regional cerebral blood flow during painful proximal gastric distention in hypersensitive FD. Methods: Brain 15Vandenberghe J. Dupont P. Fischler B. Bormans G. Persoons P. Janssens J. Tack J. Regional brain activation during proximal stomach distention in humans: a positron emission tomography study.Gastroenterology. 2005; 128: 564-573Abstract Full Text Full Text PDF Scopus (104) Google ScholarO-water positron emission tomography was performed in 13 FD patients with symptoms of gastric hypersensitivity during 3 conditions: no distention, sham distention, and isobaric distention to unpleasant or painful sensation. Pain, discomfort, nausea, and bloating during maximal distention were rated on visual analogue scales. Data were analyzed using statistical parametric mapping. Results: The threshold for painful distention was 6.6 ± 3.8 mm Hg greater than the minimal distending pressure. At the corrected P level of less than .05, subtraction analysis (painful distention - no distention) showed activations in bilateral gyrus precentralis, bilateral gyrus frontalis inferior, bilateral gyrus frontalis medialis, bilateral gyrus temporalis superior, bilateral cerebellar hemisphere, and left gyrus temporalis inferior. Sham distention minus no distention showed no activations. Conclusions: Similar to healthy volunteers, proximal stomach distention in FD activates components of the lateral pain system and bilateral frontal inferior gyri, putatively involved in regulation of hunger and satiety. In hypersensitive FD, these activations occur at significantly lower distention pressures. In contrast to findings in normosensitivity, none of the components of the medial pain system were significantly activated. Background & Aims: Hypersensitivity to proximal gastric distention as a result of abnormal central nervous system processing of visceral stimuli is a possible pathophysiologic mechanism in functional dyspepsia (FD). Increasing evidence suggests involvement of both lateral and medial pain systems in normal visceral sensitivity and aberrant brain activation patterns in visceral hypersensitivity. We hypothesized that there is involvement of aberrant brain activation in FD with hypersensitivity to gastric distention. Our aim was to investigate regional cerebral blood flow during painful proximal gastric distention in hypersensitive FD. Methods: Brain 15Vandenberghe J. Dupont P. Fischler B. Bormans G. Persoons P. Janssens J. Tack J. Regional brain activation during proximal stomach distention in humans: a positron emission tomography study.Gastroenterology. 2005; 128: 564-573Abstract Full Text Full Text PDF Scopus (104) Google ScholarO-water positron emission tomography was performed in 13 FD patients with symptoms of gastric hypersensitivity during 3 conditions: no distention, sham distention, and isobaric distention to unpleasant or painful sensation. Pain, discomfort, nausea, and bloating during maximal distention were rated on visual analogue scales. Data were analyzed using statistical parametric mapping. Results: The threshold for painful distention was 6.6 ± 3.8 mm Hg greater than the minimal distending pressure. At the corrected P level of less than .05, subtraction analysis (painful distention - no distention) showed activations in bilateral gyrus precentralis, bilateral gyrus frontalis inferior, bilateral gyrus frontalis medialis, bilateral gyrus temporalis superior, bilateral cerebellar hemisphere, and left gyrus temporalis inferior. Sham distention minus no distention showed no activations. Conclusions: Similar to healthy volunteers, proximal stomach distention in FD activates components of the lateral pain system and bilateral frontal inferior gyri, putatively involved in regulation of hunger and satiety. In hypersensitive FD, these activations occur at significantly lower distention pressures. In contrast to findings in normosensitivity, none of the components of the medial pain system were significantly activated. See Sayuk GS et al on page 556 in the May 2007 issue of CGH See Sayuk GS et al on page 556 in the May 2007 issue of CGH Visceral hypersensitivity, a condition characterized by lowered thresholds for discomfort, pain, or other sensations during intraluminal balloon distention, has been shown in several functional gastrointestinal disorders including functional dyspepsia (FD),1Bradette M. Pare P. Douville P. Morin A. Visceral perception in health and functional dyspepsia Crossover study of gastric distension with placebo and domperidone.Dig Dis Sci. 1991; 36: 52-58Google Scholar, 2Mearin F. Cucala M. Azpiroz F. Malagelada J.R. The origin of symptoms on the brain-gut axis in functional dyspepsia.Gastroenterology. 1991; 101: 999-1006Google Scholar irritable bowel syndrome (IBS),3Whitehead W.E. Holtkotter B. Enck P. Hoelzl R. Holmes K.D. Anthony J. Shabsin H.S. Schuster M.M. 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In a factor analysis of pathophysiologic and psychosocial features of FD, we found that gastric hypersensitivity was associated with several psychologic variables including the presence of anxiety, somatization, neuroticism, and a history of abuse.10Fischler B. Tack J. De Gucht V. Shkedy Z.I. Persoons P. Broekaert D. Molenberghs G. Janssens J. Heterogeneity of symptom pattern, psychosocial factors, and pathophysiological mechanisms in severe functional dyspepsia.Gastroenterology. 2003; 124: 903-910Google Scholar, 11Van Oudenhove L, Vandenberghe J, Geeraerts B, Vos R, Persoons P, Demyttenaere K, Fischler B, Tack J. The relationship between anxiety and gastric sensorimotor function in functional dyspepsia. Psychosomatic Medicine. In press.Google Scholar, 12Geeraerts B, Van Oudenhove L, Fischler B, Vandenberghe J, Caenepeel P, Janssens J, Tack J. The association between gastric sensorimotor function and abuse history in functional dyspepsia. 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Munakata J. et al.Cerebral activation in irritable bowel syndrome patients and control subjects during rectosigmoid stimulation.Psychosom Med. 2001; 63: 365-375Google Scholar We hypothesized that FD patients with hypersensitivity to gastric distention also would display altered brain activation patterns during distention of the proximal stomach. The aim of this study was to describe the brain regions activated by actual painful distention of the proximal stomach in FD with gastric hypersensitivity, and the brain regions activated by sham distention. Furthermore, this study aimed to contribute to the characterization of brain activation patterns and specific neurocircuitry associated with visceral hypersensitivity, to the elucidation of gastric sensory processing in FD, and to the understanding of the physiopathology of gastric hypersensitivity. For the latter purpose, we compared the data of the present study with recently reported findings obtained from healthy volunteers using a similar study design.15Vandenberghe J. Dupont P. Fischler B. Bormans G. Persoons P. Janssens J. Tack J. Regional brain activation during proximal stomach distention in humans: a positron emission tomography study.Gastroenterology. 2005; 128: 564-573Abstract Full Text Full Text PDF Scopus (104) Google Scholar Thirteen FD patients (3 men; mean age, 30.6 ± 8.2 y) were recruited for the study (Table 1). They were selected on the basis of demonstrated gastric hypersensitivity in a previous barostat examination (n = 8) or on the basis of a symptom pattern suggestive of gastric hypersensitivity, with epigastric pain as the predominant symptom (n = 5). Hypersensitivity, defined as a threshold for pain or unpleasantness of less than 6.4 mm Hg above minimal distending pressure,7Tack J. Caenepeel P. Fischler B. Piessevaux H. Janssens J. Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia.Gastroenterology. 2001; 121: 526-535Google Scholar was confirmed in 3 patients of the latter group. The most prevalent symptom was postprandial fullness (92%), followed by pain (85%), bloating (85%), nausea (77%), and belching (69%). Early satiety was present in 62% of the patients, whereas 54% complained of epigastric burning and 38% reported vomiting. Nine patients (69%) reported weight loss of more than 5% of their original body weight (average, 8.2 ± 2.5 kg weight decrease). All patients were Helicobacter pylori negative. Patients on psychotropic drugs were excluded from the study. All other medications potentially influencing gastrointestinal motility and sensitivity (mainly prokinetic and antinausea drugs) were discontinued at least 24 hours before study participation. None of the patients had a history of a nonfunctional gastrointestinal disease. All study procedures were undertaken with the understanding of and after obtaining written consent from each subject, in accordance with the Declaration of Human Rights (Helsinki, 1975). The protocol had been approved previously by the ethical committee of the University Hospital.Table 1Comparison of Healthy Volunteers and Hypersensitive FD PatientsHealthy volunteers (n = 11)FD patients (n = 13)P valueAge23.1 ± 1.730.6 ± 8.2.008Sex distribution (% males)45.523.1.21Threshold for painful or unpleasant sensation (mm Hg above minimal distending pressure)11.3 ± 3.46.6 ± 3.8.0040–6 rating scale score for highest distention during PET experiment4.7 ± 0.55.2 ± 0.5.07VAS score for pain5.0 ± 2.18.0 ± 2.5.39VAS score for discomfort6.6 ± 1.48.2 ± 1.1.44VAS score for nausea3.2 ± 2.86.2 ± 3.2.28VAS score for bloating8.1 ± 0.97.5 ± 3.2.67VAS score for anxiety immediately after PET experiment1.7 ± 1.31.6 ± 2.3.45VAS score for tension immediately after PET experiment2.0 ± 1.42.3 ± 2.9.37NOTE. Healthy volunteer data are from Vandenberghe et al15Vandenberghe J. Dupont P. Fischler B. Bormans G. Persoons P. Janssens J. Tack J. Regional brain activation during proximal stomach distention in humans: a positron emission tomography study.Gastroenterology. 2005; 128: 564-573Abstract Full Text Full Text PDF Scopus (104) Google Scholar and hypersensitive FD patient data are from the present study. Data were compared with regard to age and sex distribution, maximal distention threshold, symptom scores during maximal distention, and tension and anxiety immediately after PET experiment. Open table in a new tab NOTE. Healthy volunteer data are from Vandenberghe et al15Vandenberghe J. Dupont P. Fischler B. Bormans G. Persoons P. Janssens J. Tack J. Regional brain activation during proximal stomach distention in humans: a positron emission tomography study.Gastroenterology. 2005; 128: 564-573Abstract Full Text Full Text PDF Scopus (104) Google Scholar and hypersensitive FD patient data are from the present study. Data were compared with regard to age and sex distribution, maximal distention threshold, symptom scores during maximal distention, and tension and anxiety immediately after PET experiment. After an overnight fast of at least 12 hours, and 2 hours before positron emission tomography (PET) imaging, a double-lumen polyvinyl tube (Salem sump tube 14 Ch; Sherwood Medical, Petit Rechain, Belgium) with a finely folded adherent plastic bag (capacity, 1200 mL; maximal diameter, 17 cm) was introduced through the mouth and secured to the subject's chin with adhesive tape. The position of the bag in the proximal stomach was checked fluoroscopically. The polyvinyl tube then was connected to a programmable barostat device (Barostat Distender Series II; G&J Electronics Inc., Toronto, Ontario, Canada). To unfold the bag, it was inflated with a fixed volume of 300 mL of air for 2 minutes with the study subject in a recumbent position and again deflated. The subjects then were positioned in the same condition as under the PET scanner, comfortably lying down (supine position) with slightly bent knees. Pilot studies with fluoroscopy control established that balloon distention occurs in the proximal stomach in this position. After a 30-minute adaptation period, the minimal distending pressure was first determined by increasing the intrabag pressure by 1 mm Hg every minute until a volume of 30 mL was reached.7Tack J. Caenepeel P. Fischler B. Piessevaux H. Janssens J. Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia.Gastroenterology. 2001; 121: 526-535Google Scholar This pressure level equilibrates the intra-abdominal pressure. To assess individual perception thresholds, isobaric distentions were performed in double-random staircase increments of 2 mm Hg starting from the minimal distending pressure, each lasting for 2 minutes, while the corresponding intragastric volume was recorded. Subjects were instructed to score their perception of upper-abdominal sensations at the end of every distending step using a graphic rating scale that combined verbal descriptors on a scale graded 0–6.7Tack J. Caenepeel P. Fischler B. Piessevaux H. Janssens J. Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia.Gastroenterology. 2001; 121: 526-535Google Scholar The end point of each sequence of distentions was established when the subjects reported discomfort or pain (score, 5 or 6). From the double-random staircase distentions, we obtained the individual's pressure thresholds for unpleasant or painful sensations (mean pressure inducing score, ≥5). Then the balloon was deflated and the subject and barostat device were transferred to the PET scanner, where the subject was installed in the same supine position with slightly bent knees and with the head positioned in the scanner ring. Immediately before and after the PET experiment, subjects were asked to complete visual analogue scales (VAS) (0–10) for anxiety and tension, ranging from "not anxious (tense) at all" to "most anxious (tense) I have ever felt." All demographic, physiologic, and psychologic measures were analyzed using SPSS software (SPSS Inc, Chicago, IL). All data are given as mean ± SD. Brain 15Vandenberghe J. Dupont P. Fischler B. Bormans G. Persoons P. Janssens J. Tack J. Regional brain activation during proximal stomach distention in humans: a positron emission tomography study.Gastroenterology. 2005; 128: 564-573Abstract Full Text Full Text PDF Scopus (104) Google ScholarO-water PET was performed during 3 conditions: (C1), no distention (baseline condition); (C2), actual distention to the individual thresholds for unpleasant or painful sensations (maximal distention) as determined in the preceding barostat procedure; and (C3), sham distention or simulated delivery of an anticipated stimulus. Just before the sham distention, the subject was instructed that a distention would follow, but during this condition no actual balloon distention was applied. Each condition was replicated 4 times in a pseudorandomized block design. Gastric sensation was rated with the same 0–6 graded graphic rating scale immediately after each distention. Pain, discomfort, nausea, and bloating during the most intense distention were rated retrospectively on a VAS (0–10) immediately after the PET experiment. Brain activity was monitored as the relative change in regional cerebral blood flow using the H215Vandenberghe J. Dupont P. Fischler B. Bormans G. Persoons P. Janssens J. Tack J. Regional brain activation during proximal stomach distention in humans: a positron emission tomography study.Gastroenterology. 2005; 128: 564-573Abstract Full Text Full Text PDF Scopus (104) Google ScholarO method.27Fox P.T. Mintun M.A. Raichle M.E. Miezin F.M. Allman J.M. Van Essen D.C. Mapping human visual cortex with positron emission tomography.Nature. 1986; 323: 806-809Google Scholar All measurements were performed in 3-dimensional mode with a Siemens-Cti Ecat Exact Hr+ (Siemens, Erlangen, Germany).28Brix G. Zaers J. Adam L.E. Bellemann M.E. Ostertag H. Trojan H. Haberkorn U. Doll J. Oberdorfer F. Lorenz W.J. Performance evaluation of a whole-body PET scanner using the NEMA protocol National Electrical Manufacturers Association.J Nucl Med. 1997; 38: 1614-1623Google Scholar The room was kept as quiet as possible. Each subject's head was immobilized with a foam head holder (Smither Medical Products, Akron, OH). Each subject had a catheter inserted into the left brachial vein for tracer administration. A transmission scan was taken (68Ge/Ga rod sources) to correct for attenuation. The following procedure then was repeated 12 times (12 scans; 4 conditions each replicated 3 times in each subject): 1 minute after starting intragastric balloon inflation (if applicable), an intravenous injection of 300 MBq H215Vandenberghe J. Dupont P. Fischler B. Bormans G. Persoons P. Janssens J. Tack J. Regional brain activation during proximal stomach distention in humans: a positron emission tomography study.Gastroenterology. 2005; 128: 564-573Abstract Full Text Full Text PDF Scopus (104) Google ScholarO (half-life, 123 seconds) was administered over 12 seconds. There was at least a 10-minute interval between 2 successive injections. Data acquisition (60 seconds) began as soon as the intracranial radioactivity count rate increased sharply (ie, usually about 40–60 seconds after the start of the injection). The intragastric balloon was deflated immediately after completion of the data acquisition. It was kept deflated in-between periods of data acquisition and during the baseline condition. The attenuation-corrected data were reconstructed using the re-projection algorithm.29Kinahan P. Rogers J. 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A three-dimensional statistical analysis for CBF activation studies in human brain.J Cereb Blood Flow Metab. 1992; 12: 900-918Google Scholar Global brain activity was fixed arbitrarily at 50 mL dL−1 min−1.34Friston K. Holmes A. Worsley K. Poline J. Frith C. Statistical parametric maps in human functional imaging: a general linear approach.Hum Brain Map. 1995; 23: 189-210Google Scholar The condition and covariate effects were estimated according to the general linear model at each voxel. To determine the activation in the distention and sham conditions relative to baseline, activity in the latter condition was subtracted from that in the distention or sham condition. For each contrast, the resulting set of voxel values constitutes a statistical parametric map of the t-statistic statistical parametric mapping (t). For the analysis, the significance threshold was set at Puncorrected < .001 (at the voxel level). However, we considered only those clusters reaching significance at the PFWE-corrected < .05 cluster level (corrected for multiple comparisons using the Family Wise Error Correction in SPM2). These clusters and their respective Pcorrected values are listed in Table 2, together with the associated Montreal Neurological Institute coordinates of the corresponding local maxima, the respective Pcorrected and t values of these local maxima, its tentative anatomic localization, and the number of voxels in the cluster.Table 2Statistical Parametric Mapping Analysis of Activation Pattern (Local Maxima and Corresponding Clusters) During Maximal Distention Relative to Baseline (C2–C1)Coordinate of local maximum (x, y, z in mm)Pcorrected (voxel level)T-value (voxel level)Tentative anatomic localizatio
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