Gastric sensitivity and reflexes: Basic mechanisms underlying clinical problems

Journal of Gastroenterology

Volumn 49, Issue 2, 2014, Pages 206-218

  Azpiroz, Fernando ^a,b   Feinle Bisset, Christine ^c   Grundy, David ^d   Tack, Jan ^e  

^a HOSPITAL UNIVERSITARI VALL D HEBRON   (Spain)

^b UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^c UNIVERSITY OF ADELAIDE   (Australia)

^d UNIVERSITY OF SHEFFIELD   (United Kingdom)

^e UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

Abdominal pain; Antral peristalsis; Functional dyspepsia; Gastric accommodation; Gastric motility; Gastric receptors; Gastric reflexes; Gastric sensitivity; Gastric tone; Gastroparesis

Indexed keywords

CAPSAICIN; CHOLECYSTOKININ; ERYTHROMYCIN; G PROTEIN COUPLED RECEPTOR; GLUCAGON; LOXIGLUMIDE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE INHIBITOR; SLOW ADAPTING RECEPTOR; TETRAHYDROLIPSTATIN; VASOACTIVE INTESTINAL POLYPEPTIDE;

ANTERIOR CINGULATE; BAROSTAT; CAUDATE NUCLEUS; CEREBELLUM; CLINICAL RESEARCH; COLD; DUMPING SYNDROME; DYSPEPSIA; EPIGASTRIC DISCOMFORT; FOOD INTAKE; FUNCTIONAL NEUROIMAGING; GASTRIC BALLOON; GASTRIC REFLEX; GASTRIC SENSITIVITY; GASTROINTESTINAL TRACT; HUMAN; HYPERSENSITIVITY; IN VIVO STUDY; INFERIOR MESENTERIC GANGLION; INTESTINE DISTENSION; INTESTINE PRESSURE; IRRITABLE COLON; LAMINA PROPRIA; MECHANICAL STRESS; MECHANORECEPTOR; MECHANOTRANSDUCTION; MOTOR PERFORMANCE; MUSCLE CONTRACTION; MUSCLE DENERVATION; MUSCLE MASS; NAUSEA; NERVE ENDING; NONHUMAN; OCCIPITAL CORTEX; OSMOLARITY; PATHOGENESIS; PATHOPHYSIOLOGY; PERCEPTION; PERIAQUEDUCTAL GRAY MATTER; POSTCENTRAL GYRUS; PRESSURE AND TENSION; PREVALENCE; PRIORITY JOURNAL; QUESTIONNAIRE; RECEPTOR POTENTIAL; REFLEX; REGULATORY MECHANISM; REVIEW; SENSORY NERVE; SENSORY RECEPTOR; SKELETAL MUSCLE; SOLITARY TRACT NUCLEUS; STIMULUS; STOMACH ACID SECRETION; STOMACH DISEASE; STOMACH DISTENSION; STOMACH EMPTYING; STOMACH FUNCTION; STOMACH MUCOSA; STOMACH MUSCLE; STOMACH PARESIS; STOMACH PRESSURE; STOMACH SECRETION; STOMACH WALL; SWALLOWING; TENDON RECEPTOR; VAGUS NERVE; WATER SUPPLY;

ANIMALS; DYSPEPSIA; GASTRIC EMPTYING; GASTROPARESIS; HUMANS; MUSCLE CONTRACTION; MUSCLE RELAXATION; MUSCLE TONUS; PERCEPTION; REFLEX, ABNORMAL; STOMACH; VISCERAL AFFERENTS;

EID: 84896704875     PISSN: 09441174     EISSN: 14355922     Source Type: Journal    
DOI: 10.1007/s00535-013-0917-8     Document Type: Review

References (117)

1. Ehrlein HJ, Schemann M. Influence of food constituents. In: Van Nueten JM, Schuurkes JAJ, Akkermans LMA, editors. Gastro-pyloro-duodenal coordination. Petersfield: Wrightson Biomedical Publishing Ltd; 1990. p. 139-51.
2. Code CF, Marlett JA. The interdigestive myo-electric complex of the stomach and small bowel of dogs. J Physiol. 1975;246:289-309.
3. Feinle-Bisset C, O'Donovan DG, Horowitz M. Gastric motility. In: Johnson LR, editor. Encyclopedia of Gastroenterology. USA: Elsevier; 2004. p. 132-8.
4. Azpiroz F, Malagelada JR. Intestinal control of gastric tone. Am J Physiol. 1985;249:G501-9.
5. Faas H, Hebbard GS, Feinle C, et al. Pressure-geometry relationship in the antroduodenal region in humans. Am J Physiol Gastrointest Liver Physiol. 2001;281:G1214-20.
6. Heddle R, Collins PJ, Dent J, et al. Motor mechanisms associated with slowing of the gastric emptying of a solid meal by an intraduodenal lipid infusion. J Gastroenterol Hepatol. 1989;4:437-47.
7. Malagelada Prats C, Mendez S, Accarino AM, et al. Digestive, cognitive and hedonistic responses to meal ingestion. Neurogastroenterol Motil. 2012;24(Suppl s2):98.
8. Parkman HP, Hasler WL, Fisher RS. American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology. 2004;127:1592-622.
9. Miwa H. Why dyspepsia can occur without organic disease: pathogenesis and management of functional dyspepsia. J Gastroenterol. 2012;47:862-71.
10. Feinle-Bisset C, Azpiroz F. Dietary and lifestyle factors in functional dyspepsia. Nat Rev Gastroenterol Hepatol. 2013;10:150-7.
11. Tack J, Talley NJ, Camilleri M, et al. Functional gastroduodenal disorders. Gastroenterology. 2006;130:1466-79.
12. Azpiroz F, Tack J. Gastric disorders. In: Spiller R, Grundy D, editors. Pathophysiology of the enteric nervous system: a basis for understanding functional diseases. USA: Wiley-Blackwell; 2004. p. 126-33.
13. Quartero AO, de Wit NJ, Lodder AC, et al. Disturbed solid-phase gastric emptying in functional dyspepsia: a meta-analysis. Dig Dis Sci. 1998;43:2028-33.
14. Stevens JE, Jones KL, Rayner CK, et al. Pathophysiology and pharmacotherapy of gastroparesis: current and future perspectives. Expert Opin Pharmacother. 2013;14:1171-86.
15. Sturm A, Holtmann G, Goebell H, et al. Prokinetics in patients with gastroparesis: a systematic analysis. Digestion. 1999;60:422-7.
16. Tack J, Bisschops R, Sarnelli G. Pathophysiology and treatment of functional dyspepsia. Gastroenterology. 2004;127:1239-55.
17. Stanghellini V, Tosetti C, Paternico A, et al. Risk indicators of delayed gastric emptying of solids in patients with functional dyspepsia. Gastroenterology. 1996;110:1036-42.
18. Azpiroz F, Malagelada JR. Gastric tone measured by an electronic barostat in health and postsurgical gastroparesis. Gastroenterology. 1987;92:934-43.
19. Tack J. The difficult patient with gastroparesis. Best Pract Res Clin Gastroenterol. 2007;21:379-91.
20. Delgado-Aros S, Camilleri M, Cremonini F, et al. Contributions of gastric volumes and gastric emptying to meal size and postmeal symptoms in functional dyspepsia. Gastroenterology. 2004;127:1685-94.
21. Sarnelli G, Caenepeel P, Geypens B, et al. Symptoms associated with impaired gastric emptying of solids and liquids in functional dyspepsia. Am J Gastroenterol. 2003;98:783-8.
22. Piessevaux H, Tack J, Walrand S, et al. Intragastric distribution of a standardized meal in health and functional dyspepsia: correlation with specific symptoms. Neurogastroenterol Motil. 2003;15:447-55.
23. Tack J, Bisschops R. Mechanisms underlying meal-induced symptoms in functional dyspepsia. Gastroenterology. 2004;127:1844-7.
24. Azpiroz F, Malagelada JR. Physiological variations in canine gastric tone measured by an electronic barostat. Am J Physiol. 1985;248:G229-37.
25. Caldarella MP, Azpiroz F, Malagelada JR. Antro-fundic dysfunctions in functional dyspepsia. Gastroenterology. 2003;124:1220-9.
26. Lee KJ, Vos R, Janssens J, et al. Differences in the sensorimotor response to distension between the proximal and distal stomach in humans. Gut. 2004;53:938-43.
27. Szurszewski JH. Electrical basis for gastrointestinal motility. In: Johnson LR, editor. Physiology of the gastrointestinal tract. New York: Raven Press; 1981. p. 1435-66.
28. Azpiroz F, Malagelada JR. Pressure activity patterns in the canine proximal stomach: response to distension. Am J Physiol. 1984;247:G265-72.
29. Cuomo R, Vandaele P, Coulie B, et al. Influence of motilin on gastric fundus tone and on meal-induced satiety in man: role of cholinergic pathways. Am J Gastroenterol. 2006;101:804-11.
30. Simren M, Vos R, Janssens J, et al. Unsuppressed postprandial phasic contractility in the proximal stomach in functional dyspepsia: relevance to symptoms. Am J Gastroenterol. 2003;98:2169-75.
31. Carrasco M, Azpiroz F, Malagelada JR. Modulation of gastric accommodation by duodenal nutrients. World J Gastroenterol. 2005;11:4848-51.
32. Feinle C, Christen M, Grundy D, et al. Effects of duodenal fat, protein or mixed-nutrient infusions on epigastric sensations during sustained gastric distension in healthy humans. Neurogastroenterol Motil. 2002;14:205-13.
33. Feinle C, Rades T, Otto B, et al. Fat digestion modulates gastrointestinal sensations induced by gastric distention and duodenal lipid in humans. Gastroenterology. 2001;120:1100-7.
34. Di Stefano M, Vos R, Klersy C, et al. Neostigmine-induced postprandial phasic contractility in the proximal stomach and dyspepsia-like symptoms in healthy volunteers. Am J Gastroenterol. 2006;101:2797-804.
35. Azpiroz F, Malagelada JR. Vagally mediated gastric relaxation induced by intestinal nutrients in the dog. Am J Physiol. 1986;251:G727-35.
36. Azpiroz F, Malagelada JR. Importance of vagal input in maintaining gastric tone in the dog. J Physiol. 1987;384:511-24.
37. Barbier AJ, Lefebvre RA. Involvement of the l-arginine: nitric oxide pathway in nonadrenergic noncholinergic relaxation of the cat gastric fundus. J Pharmacol Exp Ther. 1993;266:172-8.
38. Desai KM, Sessa WC, Vane JR. Involvement of nitric oxide in the reflex relaxation of the stomach to accommodate food or fluid. Nature. 1991;351:477-9.
39. Grider JR, Cable MB, Said SI, et al. Vasoactive intestinal peptide as a neural mediator of gastric relaxation. Am J Physiol. 1985;248:G73-8.
40. Grundy D, Gharib-Naseri MK, Hutson D. Role of nitric oxide and vasoactive intestinal polypeptide in vagally mediated relaxation of the gastric corpus in the anaesthetized ferret. J Auton Nerv Syst. 1993;43:241-6.
41. Li CG, Rand MJ. Nitric oxide and vasoactive intestinal polypeptide mediate non-adrenergic, non-cholinergic inhibitory transmission to smooth muscle of the rat gastric fundus. Eur J Pharmacol. 1990;191:303-9.
42. Meulemans AL, Eelen JG, Schuurkes JA. NO mediates gastric relaxation after brief vagal stimulation in anesthetized dogs. Am J Physiol. 1995;269:G255-61.
43. Takahashi T, Owyang C. Vagal control of nitric oxide and vasoactive intestinal polypeptide release in the regulation of gastric relaxation in rat. J Physiol. 1995;484(Pt 2):481-92.
44. Tonini M, De Giorgio R, De Ponti F, et al. Role of nitric oxide- and vasoactive intestinal polypeptide-containing neurones in human gastric fundus strip relaxations. Br J Pharmacol. 2000;129:12-20.
45. Kuiken SD, Vergeer M, Heisterkamp SH, et al. Role of nitric oxide in gastric motor and sensory functions in healthy subjects. Gut. 2002;51:212-8.
46. Tack J, Demedts I, Meulemans A, et al. Role of nitric oxide in the gastric accommodation reflex and in meal induced satiety in humans. Gut. 2002;51:219-24.
47. De Ponti F, Azpiroz F, Malagelada JR. Reflex gastric relaxation in response to distention of the duodenum. Am J Physiol. 1987;252:G595-601.
48. Andrews PL, Scratcherd T. The gastric motility patterns induced by direct and reflex excitation of the vagus nerves in the anaesthetized ferret. J Physiol. 1980;302:363-78.
49. Troncon LE, Thompson DG, Ahluwalia NK, et al. Relations between upper abdominal symptoms and gastric distension abnormalities in dysmotility like functional dyspepsia and after vagotomy. Gut. 1995;37:17-22.
50. Farre R, Tack J. Food and symptom generation in functional gastrointestinal disorders: physiological aspects. Am J Gastroenterol. 2013;108:698-706.
51. Grundy D. Neuroanatomy of visceral nociception: vagal and splanchnic afferent. Gut. 2002;51(Suppl 1):i2-5.
52. de Jonge WJ, van den Wijngaard RM, The FO, et al. Postoperative ileus is maintained by intestinal immune infiltrates that activate inhibitory neural pathways in mice. Gastroenterology. 2003;125:1137-47.
53. Andrews PL, Sanger GJ. Abdominal vagal afferent neurones: an important target for the treatment of gastrointestinal dysfunction. Curr Opin Pharmacol. 2002;2:650-6.
54. Gebhart GF. Descending modulation of pain. Neurosci Biobehav Rev. 2004;27:729-37.
55. Berthoud HR, Neuhuber WL. Functional and chemical anatomy of the afferent vagal system. Auton Neurosci. 2000;85:1-17.
56. Stewart JE, Feinle-Bisset C, Keast RS. Fatty acid detection during food consumption and digestion: associations with ingestive behavior and obesity. Prog Lipid Res. 2011;50:225-33.
57. Grundy D. What activates visceral afferents? Gut. 2004;53(Suppl 2):ii5-8.
58. Blackshaw LA, Grundy D, Scratcherd T. Vagal afferent discharge from gastric mechanoreceptors during contraction and relaxation of the ferret corpus. J Auton Nerv Syst. 1987;18:19-24.
59. Ozaki N, Gebhart GF. Characterization of mechanosensitive splanchnic nerve afferent fibers innervating the rat stomach. Am J Physiol Gastrointest Liver Physiol. 2001;281:G1449-59.
60. Ozaki N, Sengupta JN, Gebhart GF. Mechanosensitive properties of gastric vagal afferent fibers in the rat. J Neurophysiol. 1999;82:2210-20.
61. Bielefeldt K, Ozaki N, Gebhart GF. Mild gastritis alters voltage-sensitive sodium currents in gastric sensory neurons in rats. Gastroenterology. 2002;122:752-61.
62. Vandenberghe J, Vos R, Persoons P, et al. Dyspeptic patients with visceral hypersensitivity: sensitisation of pain specific or multimodal pathways? Gut. 2005;54:914-9.
63. Coffin B, Chollet R, Flourie B, et al. Intraluminal modulation of gastric sensitivity to distension: effects of hydrochloric acid and meal. Am J Physiol Gastrointest Liver Physiol. 2001;280:G904-9.
64. Lee KJ, Vos R, Tack J. Effects of capsaicin on the sensorimotor function of the proximal stomach in humans. Aliment Pharmacol Ther. 2004;19:415-25.
65. Holzer P. Taste receptors in the gastrointestinal tract. V. Acid sensing in the gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol. 2007;292:G699-705.
66. Powley TL, Phillips RJ. Musings on the wanderer: what's new in our understanding of vago-vagal reflexes? I. Morphology and topography of vagal afferents innervating the GI tract. Am J Physiol Gastrointest Liver Physiol. 2002;283:G1217-25.
67. Zagorodnyuk VP, Chen BN, Brookes SJ. Intraganglionic laminar endings are mechano-transduction sites of vagal tension receptors in the guinea-pig stomach. J Physiol. 2001;534:255-68.
68. Distrutti E, Azpiroz F, Soldevilla A, et al. Gastric wall tension determines perception of gastric distention. Gastroenterology. 1999;116:1035-42.
69. Notivol R, Coffin B, Azpiroz F, et al. Gastric tone determines the sensitivity of the stomach to distention. Gastroenterology. 1995;108:330-6.
70. Piessevaux H, Tack J, Wilmer A, et al. Perception of changes in wall tension of the proximal stomach in humans. Gut. 2001;49:203-8.
71. Feinle C, D'Amato M, Read NW. Cholecystokinin-A receptors modulate gastric sensory and motor responses to gastric distension and duodenal lipid. Gastroenterology. 1996;110:1379-85.
72. Distrutti E, Salvioli B, Azpiroz F, et al. Rectal function and bowel habit in irritable bowel syndrome. Am J Gastroenterol. 2004;99:131-7.
73. Harder H, Serra J, Azpiroz F, et al. Reflex control of intestinal gas dynamics and tolerance in humans. Am J Physiol Gastrointest Liver Physiol. 2004;286:G89-94.
74. Serra J, Azpiroz F, Malagelada JR. Perception and reflex responses to intestinal distention in humans are modified by simultaneous or previous stimulation. Gastroenterology. 1995;109:1742-9.
75. Khan MI, Read NW, Grundy D. Effect of varying the rate and pattern of gastric distension on its sensory perception and motor activity. Am J Physiol. 1993;264:G824-7.
76. Morrison JF. Splanchnic slowly adapting mechanoreceptors with punctate receptive fields in the mesentery and gastrointestinal tract of the cat. J Physiol. 1973;233:349-61.
77. Miller SM, Szurszewski JH. Colonic mechanosensory afferent input to neurons in the mouse superior mesenteric ganglion. Am J Physiol. 1997;272:G357-66.
78. Miller SM, Szurszewski JH. Relationship between colonic motility and cholinergic mechanosensory afferent synaptic input to mouse superior mesenteric ganglion. Neurogastroenterol Motil. 2002;14:339-48.
79. De Wever I, Eeckhout C, Vantrappen G, et al. Disruptive effect of test meals on interdigestive motor complex in dogs. Am J Physiol. 1978;235:E661-5.
80. Rees WD, Malagelada JR, Miller LJ, et al. Human interdigestive and postprandial gastrointestinal motor and gastrointestinal hormone patterns. Dig Dis Sci. 1982;27:321-9.
81. Barbera R, Feinle C, Read NW. Abnormal sensitivity to duodenal lipid infusion in patients with functional dyspepsia. Eur J Gastroenterol Hepatol. 1995;7:1051-7.
82. Coffin B, Azpiroz F, Guarner F, et al. Selective gastric hypersensitivity and reflex hyporeactivity in functional dyspepsia. Gastroenterology. 1994;107:1345-51.
83. Tack J, Piessevaux H, Coulie B, et al. Role of impaired gastric accommodation to a meal in functional dyspepsia. Gastroenterology. 1998;115:1346-52.
84. Moragas G, Azpiroz F, Pavia J, et al. Relations among intragastric pressure, postcibal perception, and gastric emptying. Am J Physiol. 1993;264:G1112-7.
85. Caldarella MP, Azpiroz F, Malagelada JR. Selective effects of nutrients on gut sensitivity and reflexes. Gut. 2007;56:37-42.
86. Azpiroz F, Salvioli B. Barostat measurements. In: Schuster MM, Crowel MD, Koch KL, editors. Schuster Atlas of Gastrointestinal Motility in Health and Disease. Hamilto: BC Decker; 2002. p. 151-70.
87. Troncon LE, Bennett RJ, Ahluwalia NK, et al. Abnormal intragastric distribution of food during gastric emptying in functional dyspepsia patients. Gut. 1994;35:327-32.
88. Grundy D, Hutson D, Rudge LJ, et al. Pre-pyloric mechanisms regulating gastric motor function in the conscious dog. Q J Exp Physiol. 1989;74:857-65.
89. Villanova N, Azpiroz F, Malagelada JR. Gastrogastric reflexes regulating gastric tone and their relationship to perception. Am J Physiol. 1997;273:G464-9.
90. Feinle C, Grundy D, Read NW. Effects of duodenal nutrients on sensory and motor responses of the human stomach to distension. Am J Physiol. 1997;273:G721-6.
91. Feinle C, Meier O, Otto B, et al. Role of duodenal lipid and cholecystokinin A receptors in the pathophysiology of functional dyspepsia. Gut. 2001;48:347-55.
92. Demarchi B, Vos R, Deprez P, et al. Influence of a lipase inhibitor on gastric sensitivity and accommodation to an orally ingested meal. Aliment Pharmacol Ther. 2004;19:1261-8.
93. Villanova N, Azpiroz F, Malagelada JR. Perception and gut reflexes induced by stimulation of gastrointestinal thermoreceptors in humans. J Physiol. 1997;502(Pt 1):215-22.
94. Azpiroz F, Malagelada JR. Isobaric intestinal distension in humans: sensorial relay and reflex gastric relaxation. Am J Physiol. 1990;258:G202-7.
95. Barbera R, Feinle C, Read NW. Nutrient-specific modulation of gastric mechanosensitivity in patients with functional dyspepsia. Dig Dis Sci. 1995;40:1636-41.
96. Lee KJ, Vos R, Janssens J, et al. Influence of duodenal acidification on the sensorimotor function of the proximal stomach in humans. Am J Physiol Gastrointest Liver Physiol. 2004;286:G278-84.
97. Saperas E, Azpiroz F, Cucala M, et al. Postcibal secretory and symptomatic responses to increased intragastric pressure. Neurogastroenterol Motil. 1994;6:295-301.
98. Rao SS, Vemuri S, Harris B, et al. Fundic balloon distension stimulates antral and duodenal motility in man. Dig Dis Sci. 2002;47:1015-9.
99. Azpiroz F. Hypersensitivity in functional gastrointestinal disorders. Gut. 2002;51(Suppl 1):i25-8.
100. Ladabaum U, Minoshima S, Hasler WL, et al. Gastric distention correlates with activation of multiple cortical and subcortical regions. Gastroenterology. 2001;120:369-76.
101. Ladabaum U, Roberts TP, McGonigle DJ. Gastric fundic distension activates fronto-limbic structures but not primary somatosensory cortex: a functional magnetic resonance imaging study. Neuroimage. 2007;34:724-32.
102. Vandenbergh J, Dupont P, Fischler B, et al. Regional brain activation during proximal stomach distention in humans: a positron emission tomography study. Gastroenterology. 2005;128:564-73.
103. Stasi C, Rosselli M, Bellini M, et al. Altered neuro-endocrine-immune pathways in the irritable bowel syndrome: the top-down and the bottom-up model. J Gastroenterol. 2012;47:1177-85.
104. Boeckxstaens GE, Hirsch DP, Kuiken SD, et al. The proximal stomach and postprandial symptoms in functional dyspeptics. Am J Gastroenterol. 2002;97:40-8.
105. Mearin F, Cucala M, Azpiroz F, et al. The origin of symptoms on the brain-gut axis in functional dyspepsia. Gastroenterology. 1991;101:999-1006.
106. Accarino AM, Azpiroz F, Malagelada JR. Symptomatic responses to stimulation of sensory pathways in the jejunum. Am J Physiol. 1992;263:G673-7.
107. Accarino AM, Azpiroz F, Malagelada JR. Selective dysfunction of mechanosensitive intestinal afferents in irritable bowel syndrome. Gastroenterology. 1995;108:636-43.
108. Serra J, Azpiroz F, Malagelada JR. Modulation of gut perception in humans by spatial summation phenomena. J Physiol. 1998;506(Pt 2):579-87.
109. Accarino AM, Azpiroz F, Malagelada JR. Gut perception in humans is modulated by interacting gut stimuli. Am J Physiol Gastrointest Liver Physiol. 2002;282:G220-5.
110. Rouillon JM, Azpiroz F, Malagelada JR. Reflex changes in intestinal tone: relationship to perception. Am J Physiol. 1991;261:G280-6.
111. Rouillon JM, Azpiroz F, Malagelada JR. Sensorial and intestinointestinal reflex pathways in the human jejunum. Gastroenterology. 1991;101:1606-12.
112. Tack J, Caenepeel P, Corsetti M, et al. Role of tension receptors in dyspeptic patients with hypersensitivity to gastric distention. Gastroenterology. 2004;127:1058-66.
113. Accarino AM, Azpiroz F, Malagelada JR. Modification of small bowel mechanosensitivity by intestinal fat. Gut. 2001;48:690-5.
114. Lee KJ, Demarchi B, Demedts I, et al. A pilot study on duodenal acid exposure and its relationship to symptoms in functional dyspepsia with prominent nausea. Am J Gastroenterol. 2004;99:1765-73.
115. Samsom M, Verhagen MA, van Berge Henegouwen GP. Abnormal clearance of exogenous acid and increased acid sensitivity of the proximal duodenum in dyspeptic patients. Gastroenterology. 1999;116:515-20.
116. Schwartz MP, Samsom M, Smout AJ. Chemospecific alterations in duodenal perception and motor response in functional dyspepsia. Am J Gastroenterol. 2001;96:2596-602.
117. Oshima T, Okugawa T, Tomita T, et al. Generation of dyspeptic symptoms by direct acid and water infusion into the stomachs of functional dyspepsia patients and healthy subjects. Aliment Pharmacol Ther. 2012;35:175-82.