Gastric Perception Thresholds Are Low and Sensory Neuropeptide Levels High in Helicobacter pylori-Positive Functional DyspepsiaMönnikes H.a,b · van der Voort I.R.a,b · Wollenberg B.c · Heymann-Mönnikes I.b · Tebbe J.J.c · Alt W.d · Arnold R.c · Klapp B.F.b · Wiedenmann B.a · McGregor G.P.e
aDepartment of Medicine, Division of Hepatology and Gastroenterology, Charité, Campus Virchow-Klinikum, and bDepartment of Medicine, Division of Psychosomatic Medicine and Psychotherapy, Charité, Campus Charité Mitte, Humboldt-Universität zu Berlin, cDepartment of Internal Medicine, Division of Gastroenterology, Endocrinology, and Metabolic Diseases, dDepartment of Pathology, and eDepartment of Physiology, Philipps University, Marburg, Germany
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Article / Publication Details
Background and Aims: In functional dyspepsia (FD) decreased perception levels can be shown on gastric distension. Substance P (SP) and calcitonin gene-related peptide (CGRP) are involved in the sensitization of afferent neuronal pathways due to chronic inflammation. The role of Helicobacter pylori-induced gastric mucosal inflammation in the pathogenesis of FD is controversial. The aim of this study was to assess whether FD patients have altered mucosal concentrations of CGRP and SP, and to investigate whether this is associated with visceral hypersensitivity or H. pylori infection. Methods: Gastrointestinal symptoms, H. pylori status, perception thresholds at gastric balloon distension, and gastric mucosal concentrations of CGRP and SP were determined in 13 FD patients and 18 healthy controls (HC). Results: In H. pylori-positive FD patients discomfort and pain thresholds on gastric distension were lower compared to other groups. Antral mucosal levels of CGRP and SP were higher in H. pylori-positive subjects. In FD significantly negative correlations between discomfort and pain thresholds and antral mucosal concentrations of CGRP and SP were observed. Conclusions: In FD low perception thresholds on gastric distension are associated with high levels of CGRP and SP in the antrum, suggesting that sensory neuropeptides are involved in FD pathophysiology.
© 2005 S. Karger AG, Basel
- Holtmann G, Goebell H, Talley JN: Dyspepsia in consulters and non-consulters: Prevalence, healthcare seeking behavior and risk factors. Eur J Hepatol 1994;6:917–924.
- Holtmann G, Talley JN, Goebell H: Association between H. pylori, duodenal mechanosensory thresholds and small intestinal motility in chronic unexplained dyspepsia. Dig Dis Sci 1996;41:1285–1291.
- Mayer EA, Gebhart GF: Basic and clinical aspects of visceral hyperalgesia. Gastroenterology 1994;107:271–293.
- Collins SM: The immunomodulation of enteric neuromuscular function: Implications for motility and inflammatory disorders. Gastroenterology 1996;111:1683–1699.
- De Giorgio R, Barbara G, Blennerhassett P, Wang L, Stanghellini V, Corinaldesi R, Collins SM, Tougas G: Intestinal inflammation and activation of sensory nerve pathways: A functional and morphological study in the nematode infected rat. Gut 2001;49:822–827.
- Thumshirn M, Camilleri M, Saslow SB, Williams DE, Burton DD, Hanson RB: Gastric accommodation in non-ulcer dyspepsia and the role of Helicobacter pylori infection and vagal function. Gut 1999;44:55–64.
- Mearin F, De Ribot X, Balboa A, Salas A, Varas MJ, Cucala M, Bartolomé R, Armengol JR, Malagelada J-R: Does Helicobacter pylori infection increase gastric sensitivity in functional dyspepsia? Gut 1995;37:47–51.
- Stanghellini V, Barbara G, de Giorgio R, Tosetti C, Cogliandro R, Cogliandro L, Salvioli B, Corinaldesi R: Review article: Helicobacter pylori, mucosal inflammation and symptom perception – New insights into an old hypothesis. Aliment Pharmacol Ther 2001;15:28–32.
- Van Assche G, Barbara G, Deng Y, Lovato P, Gauldie J, Collins SM: Neurotransmitters modulate cytokine-stimulated interleukin 6 secretion in rat intestinal smooth muscle cells. Gastroenterology 1999;166:346–353.
- Kuraishi Y, Nanayama T, Ohno H, Fujii N, Otaka A, Yajima H, Satoh M: Calcitonin gene-related peptide increases in the dorsal root ganglia of adjuvant arthritic rat. Peptides 1989;10:447–452.
- Fischer A, McGregor GP, Saria A, Philippin B, Kummer W: Induction of tachykinin gene and peptide expression in guinea pig nodose primary afferent neurons by allergic airway inflammation. J Clin Invest 1996;98:2284–2291.
McMahon SB: NGF as a mediator of inflammatory pain. Philos Trans R Soc Lond B Biol Sci 1996;351:431–440.
- Buéno L, Fioramonti J, Delvaux M, Frexinos J: Mediators and pharmacology of visceral sensitivity: From basic to clinical investigations. Gastroenterology 1997;122:1714–1743.
Holzer P: Calcitonin gene-related peptide; in Walsh JH, Dockray GJ (eds): Gut Peptides: Biochemistry and Physiology. New York, Raven Press, 1994, pp 493–523.
- Otsuka M, Yoshioka K: Neurotransmitter functions of mammalian tachykinins. Physiol Rev 1993;73:229–308.
Holzer P: Local microcirculatory reflexes and afferent signaling in response to gastric acid challenge. Gut 2000;47(suppl 4):iv46–iv48; discussion iv52.
- Spiller RC: Role of nerves in enteric infection. Gut 2002;51:759–762.
- Sternini C, Anderson K: Calcitonin gene-related peptide-containing neurons supplying the rat digestive system: Differential distribution and expression pattern. Somatosens Mot Res 1992;9:45–59.
- Vongthavaravat V, Mesiya S, Saymeh L, Xia Y, Harty RF: Mechanisms of transforming growth factor-alpha (TGF-alpha) induced gastroprotection against ethanol in the rat: Roles of sensory neurons, sensory neuropeptides, and prostaglandins. Dig Dis Sci 2003;48:329–333.
- Holzer P, Holzer-Petsche U: Tachykinins in the gut. Part II. Roles in neural excitation, secretion and inflammation. Pharmacol Ther 1997;73:219–263.
- Julia V, Morteau O, Buéno L: Involvement of neurokinin 1 and 2 receptors in viscerosensitive response to rectal distension in rats. Gastroenterology 1994;107:94–102.
- Maggi CA: Tachykinin as peripheral modulators of primary afferent nerves and visceral sensitivity. Pharmacol Res 1997;36:153–169.
Kishimoto S, Kobayash H, Machino H, et al: High concentrations of substance P as a possible transmission of abdominal pain in rats with chemical induced ulcerative colitis. Biomed Res 1994;15:133–140.
Talley NJ, Stanghellini V, Heading RS, Koch KL, Malagelada JR, Tytgat G: Functional gastroduodenal disorders. Gut 1999;46(suppl 2):II37–II42.
- Dixon MF, Genta RM, Yardley JH, et al: Classification and grading of gastritis. The updated Sydney System. International Workshop on Histopathology of Gastritis, Houston, 1994. Am J Surg Pathol 1996;20:1161–1181.
- Lembo T, Munakata J, Naliboff B, Fullerton S, Mayer EA: Sigmoid afferent mechanisms in patients with irritable bowel syndrome. Dig Dis Sci 1997:42:1112–1120.
- Gracely RH, Kwilosz DM: The Descriptor Differential Scale: Applying psychophysical principles to clinical pain assessment. Pain 1988;35:279–288.
- McGregor GP, Bloom SR: Radioimmunoassay of substance P and its stability in tissue. Life Sci 1983;32:655–662.
- McGregor GP, Conlon JM: Regulatory peptide and serotonin content and brush-border enzyme activity in the rat gastrointestinal tract following neonatal treatment with capsaicin: Lack of effect on epithelial markers. Regul Pept 1991;32:109–120.
- Cheli R, Perasso A, Giacosa A: Dyspepsia and chronic gastritis. Hepatogastroenterology 1983;30:21–23.
- Mertz H, Fullerton S, Naliboff B, Mayer EA: Symptoms and visceral perception in severe functional and organic dyspepsia. Gut 1998;2:814–822.
- Lémann M, Dederding JP, Flourié B, Franchisseur C, Rambaud JC, Jian R: Abnormal perception of visceral pain in response to gastric distension in chronic idiopathic dyspepsia. The irritable stomach syndrome. Dig Dis Sci 1991;36:1249–1254.
- Saslow SB, Thumshirn M, Camilleri M, Locke GR III, Thomforde GM, Burton DD, Hanson RB: Influence of H. pylori infection on gastric motor and sensory function in asymptomatic volunteers. Dig Dis Sci 1998;43:258–264.
- Braden B, Caspary WF, Lembcke B: Density of gastric Helicobacter pylori colonization is not associated with occurrence of dyspeptic symptoms. Dig Dis Sci 1997;42:2120–2123.
- Buckley MJ, O’Shea J, Grace A, English L, Keane C, Hourihan D, O’Morain CA: A community-based study of the epidemiology of Helicobacter pylori infection and associated asymptomatic gastroduodenal pathology. Eur J Gastroenterol Hepatol 1998;10:375–379.
- Glasbrenner B, Weiler S, Ellenrieder V, Muller P, Adler G: Relationship between Helicobacter pylori infection, histological gastritis and functional dyspepsia. Hepatogastroenterology 1998;45:2238–2243.
- Pereira-Lima JG, Scholl J, Pinheiro JB, Pereira-Lima L, Riemann JF: Helicobacter pylori-associated gastritis: Does it play a role in functional dyspepsia? Z Gastroenterol 1995;33:421–425.
- Talley NJ: A critique of therapeutic trials in Helicobacter pylori-positive functional dyspepsia. Gastroenterology 1994;106:1174–1183.
- Armstrong D: Helicobacter pylori infection and dyspepsia. Scand J Gastroenterol 1996;31:38–47.
- Klatt S, Pieramico O, Guethner C, Glasbrenner B, Beck K, Adler G: Gastric hypersensitivity in nonulcer dyspepsia. An inconsistent finding. Dig Dis Sci 1997;42:720–723.
- Tack J, Caenepeel P, Fischler B, Piessevaux H, Janssens J: Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia. Gastroenterology 2001;121:526–535.
- Holtmann G, Gschossmann J, Buenger L, Gerken G, Talley NJ: Do changes in visceral sensory function determine the development of dyspepsia during treatment with aspirin? Gastroenterology 2002;123:1451–1458.
- Bercik P, De Giorgio R, Blennerhassett P, Verdu EF, Barbara G, Collins SM: Immune-mediated neural dysfunction in a murine model of chronic Helicobacter pylori infection. Gastroenterology 2002;123:1205–1215.
- Troncon LE, Thompson DG, Ahluwalia NK, Barlow J, Heggie L: Relations between upper abdominal symptoms and gastric distension abnormalities in dysmotility like functional dyspepsia and after vagotomy. Gut 1995;37:17–22.
Lopez GAR, Lopez de LGA, Andrush A: Comparison between gastric and esophageal mechanosensitivity in patients with functional dyspepsia. Acta Gastroenterol Latinoam 1996;26:143–147.
- Salet GAM, Samsom M, Roelofs JMM, van Berge Henegouwen GP, Smout AJPM, Akkermans LMA: Responses to gastric distension in functional dyspepsia. Gut 1998;42:823–829.
- Tack J, Piessevaux H, Coulie B, Caenepeel P, Janssens J: Role of impaired gastric accommodation to a meal in functional dyspepsia. Gastroenterology 1998;115:1346–1352.
- Smith VC, Dhatt N, Buchan AM: The innervation of the human antro-pyloric region: Organization and composition. Can J Physiol Pharmacol 2001;79:905–918.
- Kaneko H, Mitsuma T, Uchida K, Furusawa A, Morise K: Immunoreactive somatostatin, substance P, and calcitonin gene-related peptide concentrations of the human gastric mucosa in patients with nonulcer dyspepsia and peptic ulcer disease. Am J Gastroenterol 1993;88:898–904.
- Chadwick VS, Chen W, Shu D, Paulus B, Bethwaite P, Tie A, Wilson I: Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology 2002;122:1778–1783.
Wallace JL, McKnight W, Wilson TL, Del Soldato P, Cirino G: Reduction of shock-induced gastric damage by a nitric oxide-releasing aspirin derivative: Role of neutrophils. Am J Physiol 1997;273:G1246–G1251.
- Holzer P, Livingston EH, Guth PH: Sensory neurons signal for an increase in rat gastric mucosal blood flow in the face of pending acid injury. Gastroenterology 1991;101:416–423.
Holzer P: Implications of tachykinins and calcitonin gene-related peptide in inflammatory bowel disease. Digestion 1998;59:369–383.
- Chovet M: Gastrointestinal functional bowel disorders: New therapies. Curr Opin Chem Biol 2000;4:428–432.
- McLean PG, Picard C, Garcia-Villar R, More J, Fioramonti J, Bueno L: Effects of nematode infection on sensitivity to intestinal distension: Role of tachykinin NK2 receptors. Eur J Pharmacol 1997;337:279–282.
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