Advertisement

Journal of Gastroenterology

, Volume 41, Issue 11, pp 1025–1040 | Cite as

Recent insights into digestive motility in functional dyspepsia

  • Yohei Mizuta
  • Saburo Shikuwa
  • Hajime Isomoto
  • Ryosuke Mishima
  • Yuko Akazawa
  • Jun-ichi Masuda
  • Katsuhisa Omagari
  • Fuminao Takeshima
  • Shigeru Kohno
Review

Abstract

Functional gastrointestinal disorders, such as functional dyspepsia (FD) and irritable bowel syndrome, are common pathologies of the gut. FD is a clinical syndrome defined as chronic or recurrent pain or discomfort of unknown origin in the upper abdomen. The pathophysiological mechanisms responsible for FD have not been fully elucidated, but new ideas regarding its pathophysiology and the significance of the pathophysiology with respect to the symptom pattern of FD have emerged. In particular, there is growing interest in alterations in gastric motility, such as accommodation to a meal or gastric emptying, and visceral sensation in FD. The mechanisms underlying impaired gastroduodenal motor function are unclear, but possible factors include abnormal neurohormonal function, autonomic dysfunction, visceral hypersensitivity to acid or mechanical distention, Helicobacter pylori infection, acute gastrointestinal infection, psychosocial comorbidity, and stress. Although the optimum treatment for FD is not yet clearly established, acid-suppressive drugs, prokinetic agents, eradication of H. pylori, and antidepressants have been widely used in the management of patients with FD. The therapeutic efficacy of prokinetics such as itopride hydrochloride and mosapride citrate in the treatment of FD is supported by the results of relatively large and well-controlled studies. In addition, recent research has yielded new therapeutic agents and modalities for dysmotility in FD, including agonists/antagonists of various sensorimotor receptors, activation of the nitrergic pathway, kampo medicine, acupuncture, and gastric electric stimulation. This review discusses recent research on the pathophysiology of and treatment options for FD, with special attention given to digestive dysmotility.

Key words

accommodation digestive motility functional dyspepsia gastric emptying Helicobacter pylori visceral hypersensitivity 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Drossman, DA 2006The functional gastrointestinal disorders and the Rome III processGastroenterology130137790PubMedCrossRefGoogle Scholar
  2. 2.
    Koloski, NA, Talley, NJ, Boyce, PM 2000The impact of functional gastrointestinal disorders on quality of lifeAm J Gastroenterol956771PubMedCrossRefGoogle Scholar
  3. 3.
    Holtmann, G, Siffert, W, Haag, S, Mueller, N, Langkafel, M, Senf, W,  et al. 2004G-protein beta 3 subunit 825 CC genotype is associated with unexplained (functional) dyspepsiaGastroenterology1269719PubMedCrossRefGoogle Scholar
  4. 4.
    Holtmann, G, Liebregts, T, Siffert, W 2004Molecular basis of functional gastrointestinal disordersBest Pract Res Clin Gastroenterol1863340PubMedCrossRefGoogle Scholar
  5. 5.
    Hirako, M, Kamiya, T, Misu, N, Kobayashi, Y, Adachi, H, Shikano, M,  et al. 2005Impaired gastric motility and its relationship to gastrointestinal symptoms in patients with chronic renal failureJ Gastroenterol40111622PubMedCrossRefGoogle Scholar
  6. 6.
    Haag, S, Talley, NJ, Holtmann, G 2004Symptom patterns in functional dyspepsia and irritable bowel syndrome: relationship to disturbances in gastric emptying and response to a nutrient challenge in consulters and non-consultersGut53144551PubMedCrossRefGoogle Scholar
  7. 7.
    Tack, J, Bisschops, R, Sarnelli, G 2004Pathophysiology and treatment of functional dyspepsiaGastroenterology127123955PubMedCrossRefGoogle Scholar
  8. 8.
    Takahashi, T 2003Pathophysiological significance of neuronal nitric oxide synthase in the gastrointestinal tractJ Gastroenterol3842130PubMedCrossRefGoogle Scholar
  9. 9.
    Takahashi, A, Tomomasa, T, Kaneko, H, Hatori, R, Ishige, T, Suzuki, M,  et al. 2005In vivo recording of colonic motility in conscious rats with deficiency of interstitial cells of Cajal, with special reference to the effects of nitric oxide on colonic motilityJ Gastroenterol4010438PubMedCrossRefGoogle Scholar
  10. 10.
    Mizuta, Y, Takahashi, T, Owyang, C 1999Nitrergic regulation of colonic transit in ratsAm J Physiol277G2759PubMedGoogle Scholar
  11. 11.
    Mizuta, Y, Isomoto, H, Takahashi, T 2000Impaired nitrergic innervation in rat colitis induced by dextran sulfate sodiumGastroenterology11871423PubMedCrossRefGoogle Scholar
  12. 12.
    Tack, J, Demedts, I, Dehondt, G, Caenepeel, P, Fischler, B, Zandecki, M,  et al. 2002Clinical and pathophysiological characteristics of acute-onset functional dyspepsiaGastroenterology122173847PubMedCrossRefGoogle Scholar
  13. 13.
    Sarnelli, G, Vandenberghe, J, Tack, J 2004Visceral hypersensitivity in functional disorders of the upper gastrointestinal tractDig Liver Dis363716PubMedGoogle Scholar
  14. 14.
    Feinle-Bisset, C, Vozzo, R, Horowitz, M, Talley, NJ 2004Diet, food intake, and disturbed physiology in the pathogenesis of symptoms in functional dyspepsiaAm J Gastroenterol9917081PubMedCrossRefGoogle Scholar
  15. 15.
    Nishiyama, H, Mizuta, Y, Isomoto, H, Takeshima, F, Omagari, K, Miyahara, Y,  et al. 2004Chronic visceral hypersensitivity renders defecation more susceptible to stress via a serotonergic pathway in ratsDig Dis Sci497639PubMedCrossRefGoogle Scholar
  16. 16.
    Monnikes, H, Tebbe, JJ, Hildebrandt, M, Arck, P, Osmanoglou, E, Rose, M,  et al. 2001Role of stress in functional gastrointestinal disorders. Evidence for stress-induced alterations in gastrointestinal motility and sensitivityDig Dis1920111PubMedCrossRefGoogle Scholar
  17. 17.
    Sagami, Y, Shimada, Y, Tayama, J, Nomura, T, Satake, M, Endo, Y,  et al. 2004Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndromeGut5395864PubMedCrossRefGoogle Scholar
  18. 18.
    Khan, WI, Collins, SM 2006Gut motor function: immunological control in enteric infection and inflammationClin Exp Immunol14338997PubMedCrossRefGoogle Scholar
  19. 19.
    Talley, NJ, Stanghellini, V, Heading, RC, Koch, KL, Malagelada, JR, Tytgat, GN 1999Functional gastroduodenal disordersGut453742CrossRefGoogle Scholar
  20. 20.
    Tack, J, Talley, NJ, Camilleri, M, Holtmann, G, Hu, P, Malagelada, JR,  et al. 2006Functional gastroduodenal disordersGastroenterology130146679PubMedCrossRefGoogle Scholar
  21. 21.
    Suzuki, H, Nishizawa, T, Hibi, T 2006Therapeutic strategies for functional dyspepsia and the introduction of the Rome III classificationJ Gastroenterol4151323PubMedCrossRefGoogle Scholar
  22. 22.
    Quartero, AO, de Wit, NJ, Lodder, AC, Numans, ME, Smout, AJ, Hoes, AW 1998Disturbed solid-phase gastric emptying in functional dyspepsia: a meta-analysisDig Dis Sci43202833PubMedCrossRefGoogle Scholar
  23. 23.
    Bredenoord, AJ, Chial, HJ, Camilleri, M, Mullan, BP, Murray, JA 2003Gastric accommodation and emptying in evaluation of patients with upper gastrointestinal symptomsClin Gastroenterol Hepatol126472PubMedCrossRefGoogle Scholar
  24. 24.
    Lorena, SL, Tinois, E, Brunetto, SQ, Camargo, EE, Mesquita, MA 2004Gastric emptying and intragastric distribution of a solid meal in functional dyspepsia: influence of gender and anxietyJ Clin Gastroenterol382306PubMedCrossRefGoogle Scholar
  25. 25.
    Simren, M, Vos, R, Janssens, J, Tack, J 2003Unsuppressed postprandial phasic contractility in the proximal stomach in functional dyspepsia: relevance to symptomsAm J Gastroenterol98216975PubMedGoogle Scholar
  26. 26.
    Lorena, SL, Figueiredo, MJ, Almeida, JR, Mesquita, MA 2002Autonomic function in patients with functional dyspepsia assessed by 24-hour heart rate variabilityDig Dis Sci472731PubMedCrossRefGoogle Scholar
  27. 27.
    O'Mahony, S, Dinan, TG, Keeling, PW, Chua, AS 2006Central serotonergic and noradrenergic receptors in functional dyspepsiaWorld J Gastroenterol1226817PubMedGoogle Scholar
  28. 28.
    Mattsson, H, Arani, Z, Astin, M, Bayati, A, Overstreet, DH, Lehmann, A 2005Altered neuroendocrine response and gastric dysmotility in the Flinders Sensitive Line ratNeurogastroenterol Motil1716674PubMedCrossRefGoogle Scholar
  29. 29.
    Jian, R, Ducrot, F, Ruskone, A, Chaussade, S, Rambaud, JC, Modigliani, R,  et al. 1989Symptomatic, radionuclide and therapeutic assessment of chronic idiopathic dyspepsia. A double-blind placebo-controlled evaluation of cisaprideDig Dis Sci3465764PubMedCrossRefGoogle Scholar
  30. 30.
    Sarnelli, G, Caenepeel, P, Geypens, B, Janssens, J, Tack, J 2003Symptoms associated with impaired gastric emptying of solids and liquids in functional dyspepsiaAm J Gastroenterol987838PubMedCrossRefGoogle Scholar
  31. 31.
    Kusunoki, H, Haruma, K, Hata, J, Tani, H, Okamoto, E, Sumii, K,  et al. 2000Real-time ultrasonographic assessment of antroduodenal motility after ingestion of solid and liquid meals by patients with functional dyspepsiaJ Gastroenterol Hepatol1510227PubMedCrossRefGoogle Scholar
  32. 32.
    Aoki, S, Haruma, K, Kusunoki, H, Hata, J, Hara, M, Yoshida, S,  et al. 2002Evaluation of gastric emptying measured with the 13C-octanoic acid breath test in patients with functional dyspepsia: comparison with ultrasonographyScand J Gastroenterol376626PubMedCrossRefGoogle Scholar
  33. 33.
    Talley, NJ, Shuter, B, McCrudden, G, Jones, M, Hoschl, R, Piper, DW 1989Lack of association between gastric emptying of solids and symptoms in nonulcer dyspepsiaJ Clin Gastroenterol1162530PubMedCrossRefGoogle Scholar
  34. 34.
    Talley, NJ, Verlinden, M, Jones, M 2001Can symptoms discriminate among those with delayed or normal gastric emptying in dysmotility-like dyspepsia?Am J Gastroenterol9614228PubMedCrossRefGoogle Scholar
  35. 35.
    Stanghellini, V, Tosetti, C, Paternico, A, Barbara, G, Morselli-Labate, AM, Monetti, N,  et al. 1996Risk indicators of delayed gastric emptying of solids in patients with functional dyspepsiaGastroenterology110103642PubMedCrossRefGoogle Scholar
  36. 36.
    Sarnelli, G, Grasso, R, Ierardi, E, De Giorgi, F, Savarese, MF, Russo, L,  et al. 2005Symptoms and pathophysiological correlations in patients with constipation and functional dyspepsiaDigestion7122530PubMedCrossRefGoogle Scholar
  37. 37.
    Karamanolis, G, Caenepeel, P, Arts, J, Tack, J 2006Association of the predominant symptom with clinical characteristics and pathophysiological mechanisms in functional dyspepsiaGastroenterology130296303PubMedCrossRefGoogle Scholar
  38. 38.
    Coulie, B, Tack, J, Maes, B, Geypens, B, De Roo, M, Janssens, J 1997Sumatriptan, a selective 5-HT1 receptor agonist, induces a lag phase for gastric emptying of liquids in humansAm J Physiol272G9028PubMedGoogle Scholar
  39. 39.
    Riezzo, G, Clemente, C, Leo, S, Russo, F 2005The role of electrogastrography and gastrointestinal hormones in chemotherapy-related dyspeptic symptomsJ Gastroenterol40110715PubMedCrossRefGoogle Scholar
  40. 40.
    Leahy, A, Besherdas, K, Clayman, C, Mason, I, Epstein, O 1999Abnormalities of the electrogastrogram in functional gastrointestinal disordersAm J Gastroenterol9410238PubMedCrossRefGoogle Scholar
  41. 41.
    Lin, Z, Eaker, EY, Sarosiek, I, McCallum, RW 1999Gastric myoelectrical activity and gastric emptying in patients with functional dyspepsiaAm J Gastroenterol9423849PubMedCrossRefGoogle Scholar
  42. 42.
    Holmvall, P, Lindberg, G 2002Electrogastrography before and after a high-caloric, liquid test meal in healthy volunteers and patients with severe functional dyspepsiaScand J Gastroenterol3711448PubMedCrossRefGoogle Scholar
  43. 43.
    van der Voort, IR, Osmanoglou, E, Seybold, M, Heymann-Monnikes, I, Tebbe, J, Wiedenmann, B,  et al. 2003Electrogastrography as a diagnostic tool for delayed gastric emptying in functional dyspepsia and irritable bowel syndromeNeurogastroenterol Motil1546773PubMedCrossRefGoogle Scholar
  44. 44.
    Zhang, H, Xu, X, Wang, Z, Li, C, Ke, M 2006Correlation between gastric myoelectrical activity recorded by multi-channel electrogastrography and gastric emptying in patients with functional dyspepsiaScand J Gastroenterol41797804PubMedCrossRefGoogle Scholar
  45. 45.
    Jebbink, HJ, vanBerge-Henegouwen, GP, Akkermans, LM, Smout, AJ 1996Small intestinal motor abnormalities in patients with functional dyspepsia demonstrated by ambulatory manometryGut38694700PubMedGoogle Scholar
  46. 46.
    Wilmer, A, Van Cutsem, E, Andrioli, A, Tack, J, Coremans, G, Janssens, J 1998Ambulatory gastrojejunal manometry in severe motility-like dyspepsia: lack of correlation between dysmotility, symptoms, and gastric emptyingGut4223542PubMedCrossRefGoogle Scholar
  47. 47.
    Nakamura, K, Takahashi, T, Taniuchi, M, Hsu, CX, Owyang, C 1998Nicotinic receptor mediates nitric oxide synthase expression in the rat gastric myenteric plexusJ Clin Invest101147989PubMedGoogle Scholar
  48. 48.
    Tack, J, Piessevaux, H, Coulie, B, Caenepeel, P, Janssens, J 1998Role of impaired gastric accommodation to a meal in functional dyspepsiaGastroenterology115134652PubMedCrossRefGoogle Scholar
  49. 49.
    Piessevaux, H, Tack, J, Walrand, S, Pauwels, S, Geubel, A 2003Intragastric distribution of a standardized meal in health and functional dyspepsia: correlation with specific symptomsNeurogastroenterol Motil1544755PubMedCrossRefGoogle Scholar
  50. 50.
    Kim, DY, Delgado-Aros, S, Camilleri, M, Samsom, M, Murray, JA, O'Connor, MK,  et al. 2001Noninvasive measurement of gastric accommodation in patients with idiopathic nonulcer dyspepsiaAm J Gastroenterol963099105PubMedCrossRefGoogle Scholar
  51. 51.
    Boeckxstaens, GE, Hirsch, DP, Kuiken, SD, Heisterkamp, SH, Tytgat, GN 2002The proximal stomach and postprandial symptoms in functional dyspepticsAm J Gastroenterol97408PubMedCrossRefGoogle Scholar
  52. 52.
    Tack, J, Caenepeel, P, Piessevaux, H, Cuomo, R, Janssens, J 2003Assessment of meal induced gastric accommodation by a satiety drinking test in health and in severe functional dyspepsiaGut5212717PubMedCrossRefGoogle Scholar
  53. 53.
    Monroe, MJ, Hornby, PJ, Partosoedarso, ER 2004Central vagal stimulation evokes gastric volume changes in mice: a novel technique using a miniaturized barostatNeurogastroenterol Motil16511PubMedCrossRefGoogle Scholar
  54. 54.
    Bjornsson, E, Sjoberg, J, Ringstrom, G, Norstrom, M, Simren, M, Abrahamsson, H 2003Effects of duodenal lipids on gastric sensitivity and relaxation in patients with ulcer-like and dysmotility-like dyspepsiaDigestion6720917PubMedCrossRefGoogle Scholar
  55. 55.
    Tack, J, Caenepeel, P, Corsetti, M, Janssens, J 2004Role of tension receptors in dyspeptic patients with hypersensitivity to gastric distentionGastroenterology127105866PubMedCrossRefGoogle Scholar
  56. 56.
    Hausken, T, Svebak, S, Wilhelmsen, I, Haug, TT, Olafsen, K, Pettersson, E,  et al. 1993Low vagal tone and antral dysmotility in patients with functional dyspepsiaPsychosom Med551222PubMedGoogle Scholar
  57. 57.
    Troncon, LE, Thompson, DG, Ahluwalia, NK, Barlow, J, Heggie, L 1995Relations between upper abdominal symptoms and gastric distension abnormalities in dysmotility like functional dyspepsia and after vagotomyGut371722PubMedGoogle Scholar
  58. 58.
    Armstrong, D 1996Helicobacter pylori infection and dyspepsiaScand J Gastroenterol Suppl2153847PubMedGoogle Scholar
  59. 59.
    Saruc, M, Ozden, N, Turkel, N, Ayhan, S, Demir, MA, Tuzcuoglu, I,  et al. 2003Functional dyspepsia: relationship between clinical subgroups and Helicobacter pylori status in western TurkeyBraz J Med Biol Res3674751PubMedGoogle Scholar
  60. 60.
    Danesh, J, Lawrence, M, Murphy, M, Roberts, S, Collins, R 2000Systematic review of the epidemiological evidence on Helicobacter pylori infection and nonulcer or uninvestigated dyspepsiaArch Intern Med16011928PubMedCrossRefGoogle Scholar
  61. 61.
    Kawamura, A, Adachi, K, Takashima, T, Murao, M, Katsube, T, Yuki, M,  et al. 2001Prevalence of functional dyspepsia and its relationship with Helicobacter pylori infection in a Japanese populationJ Gastroenterol Hepatol163848PubMedCrossRefGoogle Scholar
  62. 62.
    Laine, L, Schoenfeld, P, Fennerty, MB 2001Therapy for Helicobacter pylori in patients with nonulcer dyspepsia. A meta-analysis of randomized, controlled trialsAnn Intern Med1343619PubMedGoogle Scholar
  63. 63.
    Moayyedi P, Soo S, Deeks J, Delaney B, Harris A, Innes M, et al. Eradication of Helicobacter pylori for non-ulcer dyspepsia. Cochrane Database Syst Rev 2006;(2):CD002096Google Scholar
  64. 64.
    Takehara, Y, Mizuta, Y, Isomoto, H, Ohnita, K, Yoshimura, M, Nakamura, T,  et al. 2002Influence of Helicobacter pylori infection on in vitro responsiveness of gastric fundus to agonists and to stimulation of enteric nerves in Mongolian gerbilsJ Gastroenterol3758995PubMedCrossRefGoogle Scholar
  65. 65.
    Bercik, P, De Giorgio, R, Blennerhassett, P, Verdu, EF, Barbara, G, Collins, SM 2002Immune-mediated neural dysfunction in a murine model of chronic Helicobacter pylori infectionGastroenterology123120515PubMedCrossRefGoogle Scholar
  66. 66.
    Higuchi, K, Tominaga, K, Watanabe, T, Uno, H, Shiba, M, Sasaki, E,  et al. 2004Indomethacin, but not Helicobacter pylori, inhibits adaptive relaxation in isolated guinea-pig stomachDrugs Exp Clin Res3023541PubMedGoogle Scholar
  67. 67.
    Dominguez-Munoz, JE, Malfertheiner, P 2001Effect of Helicobacter pylori infection on gastrointestinal motility, pancreatic secretion and hormone release in asymptomatic humansScand J Gastroenterol3611417PubMedCrossRefGoogle Scholar
  68. 68.
    van der Schaar, PJ, Straathof, JW, Veenendaal, RA, Lamers, CB, Masclee, AA 2001Does Helicobacter pylori gastritis affect motor function of proximal stomach in dyspeptic patients?Dig Dis Sci4618338PubMedCrossRefGoogle Scholar
  69. 69.
    Thumshirn, M, Camilleri, M, Saslow, SB, Williams, DE, Burton, DD, Hanson, RB 1999Gastric accommodation in non-ulcer dyspepsia and the roles of Helicobacter pylori infection and vagal functionGut445564PubMedCrossRefGoogle Scholar
  70. 70.
    Sarnelli, G, Cuomo, R, Janssens, J, Tack, J 2003Symptom patterns and pathophysiological mechanisms in dyspeptic patients with and without Helicobacter pylori Dig Dis Sci48222936PubMedCrossRefGoogle Scholar
  71. 71.
    Koskenpato, J, Korppi-Tommola, T, Kairemo, K, Farkkila, M 2000Long-term follow-up study of gastric emptying and Helicobacter pylori eradication among patients with functional dyspepsiaDig Dis Sci4517638PubMedCrossRefGoogle Scholar
  72. 72.
    Parry, SD, Stansfield, R, Jelley, D, Gregory, W, Phillips, E, Barton, JR,  et al. 2003Does bacterial gastroenteritis predispose people to functional gastrointestinal disorders? A prospective, community-based, case–control studyAm J Gastroenterol9819705PubMedGoogle Scholar
  73. 73.
    Mearin, F, Perez-Oliveras, M, Perello, A, Vinyet, J, Ibanez, A, Coderch, J,  et al. 2005Dyspepsia and irritable bowel syndrome after a Salmonella gastroenteritis outbreak: one-year follow-up cohort studyGastroenterology12998104PubMedCrossRefGoogle Scholar
  74. 74.
    He, MR, Song, YG, Zhi, FC 2005Gastrointestinal hormone abnormalities and G and D cells in functional dyspepsia patients with gastric dysmotilityWorld J Gastroenterol114436PubMedGoogle Scholar
  75. 75.
    Feinle, C, D'Amato, M, Read, NW 1996Cholecystokinin-A receptors modulate gastric sensory and motor responses to gastric distension and duodenal lipidGastroenterology110137985PubMedCrossRefGoogle Scholar
  76. 76.
    Barbera, R, Feinle, C, Read, NW 1995Abnormal sensitivity to duodenal lipid infusion in patients with functional dyspepsiaEur J Gastroenterol Hepatol710517PubMedGoogle Scholar
  77. 77.
    Chua, AS, Keeling, PW 2006Cholecystokinin hyperresponsiveness in functional dyspepsiaWorld J Gastroenterol12268893PubMedGoogle Scholar
  78. 78.
    Chua, AS, Keeling, PW, Dinan, TG 2006Role of cholecystokinin and central serotonergic receptors in functional dyspepsiaWorld J Gastroenterol12132935PubMedGoogle Scholar
  79. 79.
    Kamerling, IM, Van Haarst, AD, Burggraaf, J, Schoemaker, RC, Biemond, I, Heinzerling, H,  et al. 2003Motilin effects on the proximal stomach in patients with functional dyspepsia and healthy volunteersAm J Physiol Gastrointest Liver Physiol284G77681PubMedGoogle Scholar
  80. 80.
    Talley, NJ, Verlinden, M, Snape, W, Beker, JA, Ducrotte, P, Dettmer, A,  et al. 2000Failure of a motilin receptor agonist (ABT-229) to relieve the symptoms of functional dyspepsia in patients with and without delayed gastric emptying: a randomized double-blind placebo-controlled trialAliment Pharmacol Ther14165361PubMedCrossRefGoogle Scholar
  81. 81.
    Date, Y, Kojima, M, Hosoda, H, Sawaguchi, A, Mondal, MS, Suganuma, T,  et al. 2000Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humansEndocrinology141425561PubMedCrossRefGoogle Scholar
  82. 82.
    Fujino, K, Inui, A, Asakawa, A, Kihara, N, Fujimura, M, Fujimiya, M 2003Ghrelin induces fasted motor activity of the gastrointestinal tract in conscious fed ratsJ Physiol55022740PubMedCrossRefGoogle Scholar
  83. 83.
    Fukuda, H, Mizuta, Y, Isomoto, H, Takeshima, F, Ohnita, K, Ohba, K,  et al. 2004Ghrelin enhances gastric motility through direct stimulation of intrinsic neural pathways and capsaicin-sensitive afferent neurones in ratsScand J Gastroenterol39120914PubMedCrossRefGoogle Scholar
  84. 84.
    Heath, RB, Jones, R, Frayn, KN, Robertson, MD 2004Vagal stimulation exaggerates the inhibitory ghrelin response to oral fat in humansJ Endocrinol18027381PubMedCrossRefGoogle Scholar
  85. 85.
    Asakawa, A, Inui, A, Kaga, T, Yuzuriha, H, Nagata, T, Fujimiya, M,  et al. 2001A role of ghrelin in neuroendocrine and behavioral responses to stress in miceNeuroendocrinology741437PubMedCrossRefGoogle Scholar
  86. 86.
    Shinomiya, T, Fukunaga, M, Akamizu, T, Irako, T, Yokode, M, Kangawa, K,  et al. 2005Plasma acylated ghrelin levels correlate with subjective symptoms of functional dyspepsia in female patientsScand J Gastroenterol4064853PubMedGoogle Scholar
  87. 87.
    Lanzini, A, Magni, P, Petroni, ML, Motta, M, Lanzarotto, F, Villanacci, V,  et al. 2006Circulating ghrelin level is increased in coeliac disease as in functional dyspepsia and reverts to normal during gluten-free dietAliment Pharmacol Ther2390713PubMedCrossRefGoogle Scholar
  88. 88.
    Takamori K, Mizuta Y, Takeshima F, Akazawa Y, Isomoto H, Ohnita K, et al. Relation among plasma ghrelin level, gastric emptying, and psychological condition in patients with functional dyspepsia. J Clin Gastroenterol 2006 (in press)Google Scholar
  89. 89.
    Tucci, A, Corinaldesi, R, Stanghellini, V, Tosetti, C, Di Febo, G, Paparo, GF,  et al. 1992Helicobacter pylori infection and gastric function in patients with chronic idiopathic dyspepsiaGastroenterology10376874PubMedGoogle Scholar
  90. 90.
    Holzer, P, Painsipp, E, Jocic, M, Heinemann, A 2003Acid challenge delays gastric pressure adaptation, blocks gastric emptying and stimulates gastric fluid secretion in the ratNeurogastroenterol Motil154555PubMedCrossRefGoogle Scholar
  91. 91.
    Samsom, M, Verhagen, MA, vanBerge Henegouwen, GP, Smout, AJ 1999Abnormal clearance of exogenous acid and increased acid sensitivity of the proximal duodenum in dyspeptic patientsGastroenterology11651520PubMedCrossRefGoogle Scholar
  92. 92.
    Lee, KJ, Vos, R, Janssens, J, Tack, J 2004Influence of duodenal acidification on the sensorimotor function of the proximal stomach in humansAm J Physiol Gastrointest Liver Physiol286G27884PubMedCrossRefGoogle Scholar
  93. 93.
    Lee, KJ, Demarchi, B, Demedts, I, Sifrim, D, Raeymaekers, P, Tack, J 2004A pilot study on duodenal acid exposure and its relationship to symptoms in functional dyspepsia with prominent nauseaAm J Gastroenterol99176573PubMedCrossRefGoogle Scholar
  94. 94.
    Schwartz, MP, Samsom, M, Smout, AJ 2001Chemospecific alterations in duodenal perception and motor response in functional dyspepsiaAm J Gastroenterol962596602PubMedCrossRefGoogle Scholar
  95. 95.
    Jones, MP, Maganti, K 2004Symptoms, gastric function, and psychosocial factors in functional dyspepsiaJ Clin Gastroenterol3886672PubMedCrossRefGoogle Scholar
  96. 96.
    Chou, LT, Wu, CY, Chen, HP, Chang, CS, Wong, PG, Ko, CW,  et al. 2001The correlation of depression and gastric dysrhythmia in functional dyspepsiaJ Clin Gastroenterol3312731PubMedCrossRefGoogle Scholar
  97. 97.
    Lorena, SL, Tinois, E, Brunetto, SQ, Camargo, EE, Mesquita, MA 2004Gastric emptying and intragastric distribution of a solid meal in functional dyspepsia: influence of gender and anxietyJ Clin Gastroenterol382306PubMedCrossRefGoogle Scholar
  98. 98.
    Tache, Y, Martinez, V, Million, M, Wang, L 2001Stress and the gastrointestinal tract III. Stress-related alterations of gut motor function: role of brain corticotropin-releasing factor receptorsAm J Physiol Gastrointest Liver Physiol280G1737PubMedGoogle Scholar
  99. 99.
    Hveem, K, Hausken, T, Svebak, S, Berstad, A 1996Gastric antral motility in functional dyspepsia. Effect of mental stress and cisaprideScand J Gastroenterol314527PubMedGoogle Scholar
  100. 100.
    Redstone, HA, Barrowman, N, Veldhuyzen Van Zanten, SJ 2001H2-receptor antagonists in the treatment of functional (nonulcer) dyspepsia: a meta-analysis of randomized controlled clinical trialsAliment Pharmacol Ther1512919PubMedCrossRefGoogle Scholar
  101. 101.
    Peura, DA, Kovacs, TO, Metz, DC, Siepman, N, Pilmer, BL, Talley, NJ 2004Lansoprazole in the treatment of functional dyspepsia: two double-blind, randomized, placebo-controlled trialsAm J Med1167408PubMedCrossRefGoogle Scholar
  102. 102.
    Talley, NJ, Meineche-Schmidt, V, Pare, P, Duckworth, M, Raisanen, P, Pap, A,  et al. 1998Efficacy of omeprazole in functional dyspepsia: double-blind, randomized, placebo-controlled trials (the Bond and Opera studies)Aliment Pharmacol Ther12105565PubMedCrossRefGoogle Scholar
  103. 103.
    Goves, J, Oldring, JK, Kerr, D, Dallara, RG, Roffe, EJ, Powell, JA,  et al. 1998First line treatment with omeprazole provides an effective and superior alternative strategy in the management of dyspepsia compared to antacid/alginate liquid: a multicentre study in general practiceAliment Pharmacol Ther1214757PubMedCrossRefGoogle Scholar
  104. 104.
    Tack, J, Caenepeel, P, Arts, J, Lee, KJ, Sifrim, D, Janssens, J 2005Prevalence of acid reflux in functional dyspepsia and its association with symptom profileGut5413706PubMedCrossRefGoogle Scholar
  105. 105.
    Schwartz, MP, Samsom, M, Van Berge Henegouwen, GP, Smout, AJ 2001Effect of inhibition of gastric acid secretion on antropyloroduodenal motor activity and duodenal acid hypersensitivity in functional dyspepsiaAliment Pharmacol Ther1519218PubMedCrossRefGoogle Scholar
  106. 106.
    Talley, NJ, Practice, Vakil N. 2005Parameters Committee of the American College of Gastroenterology. Guidelines for the management of dyspepsiaAm J Gastroenterol100232437PubMedCrossRefGoogle Scholar
  107. 107.
    Wu, CY, Chou, LT, Chen, HP, Chang, CS, Wong, PG, Chen, GH 2003Effect of fluoxetine on symptoms and gastric dysrhythmia in patients with functional dyspepsiaHepatogastroenterology5027883PubMedGoogle Scholar
  108. 108.
    Tack, J, Broekaert, D, Coulie, B, Fischler, B, Janssens, J 2003Influence of the selective serotonin re-uptake inhibitor, paroxetine, on gastric sensorimotor function in humansAliment Pharmacol Ther176038PubMedCrossRefGoogle Scholar
  109. 109.
    Hojo, M, Miwa, H, Yokoyama, T, Ohkusa, T, Nagahara, A, Kawabe, M,  et al. 2005Treatment of functional dyspepsia with antianxiety or antidepressive agents: systematic reviewJ Gastroenterol40103642PubMedCrossRefGoogle Scholar
  110. 110.
    Tonini, M, Pace, F 2006Drugs acting on serotonin receptors for the treatment of functional GI disordersDig Dis245969PubMedCrossRefGoogle Scholar
  111. 111.
    Feinle, C, Read, NW 1996Ondansetron reduces nausea induced by gastroduodenal stimulation without changing gastric motilityAm J Physiol271G5917PubMedGoogle Scholar
  112. 112.
    Talley, NJ, Van Zanten, SV, Saez, LR, Dukes, G, Perschy, T, Heath, M,  et al. 2001A dose-ranging, placebo-controlled, randomized trial of alosetron in patients with functional dyspepsiaAliment Pharmacol Ther1552537PubMedCrossRefGoogle Scholar
  113. 113.
    Kaneko, H, Konagaya, T, Kakumu, S 2006Visceral specific analgesic action of mosapride citrate, a gastroprokinetic drug, and its metabolite against gastric distension through a 5-HT4 and 5-HT3 receptor in conscious rats (abstr)Gastroenterology130A246Google Scholar
  114. 114.
    Moayyedi P, Soo S, Deeks J, Delaney B, Innes M, Forman D. Pharmacological interventions for non-ulcer dyspepsia. Cochrane Database Syst Rev 2004;(4):CD001960Google Scholar
  115. 115.
    Bouin, M, Lupien, F, Riberdy-Poitras, M, Poitras, P 2006Tolerance to gastric distension in patients with functional dyspepsia: modulation by a cholinergic and nitrergic methodEur J Gastroenterol Hepatol18638PubMedCrossRefGoogle Scholar
  116. 116.
    Tonini, M, Cipollina, L, Poluzzi, E, Crema, F, Corazza, GR, De Ponti, F 2004Review article: clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokineticsAliment Pharmacol Ther1937990PubMedCrossRefGoogle Scholar
  117. 117.
    Distrutti, E, Fiorucci, S, Hauer, SK, Pensi, MO, Vanasia, M, Morelli, A 2002Effect of acute and chronic levosulpiride administration on gastric tone and perception in functional dyspepsiaAliment Pharmacol Ther1661322PubMedCrossRefGoogle Scholar
  118. 118.
    Mearin, F, Rodrigo, L, Perez-Mota, A, Balboa, A, Jimenez, I, Sebastian, JJ,  et al. 2004Levosulpiride and cisapride in the treatment of dysmotility-like functional dyspepsia: a randomized, double-masked trialClin Gastroenterol Hepatol23018PubMedCrossRefGoogle Scholar
  119. 119.
    Stanghellini, V, De Giorgio, R, Barbara, G, Cogliandro, R, Tosetti, C, De Ponti, F,  et al. 2004Delayed gastric emptying in functional dyspepsiaCurr Treat Options Gastroenterol725964PubMedGoogle Scholar
  120. 120.
    Tack, J, Sarnelli, G 2002Serotonergic modulation of visceral sensation: upper gastrointestinal tractGut51i7780PubMedCrossRefGoogle Scholar
  121. 121.
    Boeckxstaens, GE, Hirsch, DP, Kuiken, SD, Heisterkamp, SH, Tytgat, GN 2002The proximal stomach and postprandial symptoms in functional dyspepticsAm J Gastroenterol97408PubMedCrossRefGoogle Scholar
  122. 122.
    Tack, J, Coulie, B, Wilmer, A, Andrioli, A, Janssens, J 2000Influence of sumatriptan on gastric fundus tone and on the perception of gastric distension in manGut4646873PubMedCrossRefGoogle Scholar
  123. 123.
    Tack, J, Caenepeel, P, Corsetti, M, Janssens, J 2004Role of tension receptors in dyspeptic patients with hypersensitivity to gastric distentionGastroenterology127105866PubMedCrossRefGoogle Scholar
  124. 124.
    Tack, J, Piessevaux, H, Coulie, B 1999A placebo-controlled trial of buspirone, a fundus-relaxing drug, in functional dyspepsia: effect on symptoms and gastric sensory and motor function (abstr)Gastroenterology116A325Google Scholar
  125. 125.
    Manes, G, Dominguez-Munoz, JE, Leodolter, A, Malfertheiner, P 2001Effect of cisapride on gastric sensitivity to distension, gastric compliance and duodeno-gastric reflexes in healthy humansDig Liver Dis3340713PubMedCrossRefGoogle Scholar
  126. 126.
    Talley, NJ, Vakil, NB, Moayyedi, P 2005American Gastroenterological Association technical review on the evaluation of dyspepsiaGastroenterology129175680PubMedCrossRefGoogle Scholar
  127. 127.
    Tack, J, Vos, R, Janssens, J, Salter, J, Jauffret, S, Vandeplassche, G 2003Influence of tegaserod on proximal gastric tone and on the perception of gastric distensionAliment Pharmacol Ther1810317PubMedCrossRefGoogle Scholar
  128. 128.
    Tack, J, Delia, T, Ligozio, G, Sue, S, Lefkowitz, M, Vandeplassche, G 2002A phase II placebo controlled randomized trial with tegaserod in functional dyspepsia patients with normal gastric emptying (abstr)Gastroenterology122A-154Google Scholar
  129. 129.
    Hallerback, BI, Bommelaer, G, Bredberg, E, Campbell, M, Hellblom, M, Lauritsen, K,  et al. 2002Dose finding study of mosapride in functional dyspepsia: a placebo-controlled, randomized studyAliment Pharmacol Ther1695967PubMedCrossRefGoogle Scholar
  130. 130.
    Chen, SY, Wang, JY, Zhu, CW, Yuan, YZ, Zou, B, Xia, L,  et al. 2004A randomized controlled multi-center clinical trial on mosapride in the treatment of functional dyspepsiaZhonghua Liu Xing Bing Xue Za Zhi251658PubMedGoogle Scholar
  131. 131.
    Amarapurkar, DN, Rane, P 2004Randomised, double-blind, comparative study to evaluate the efficacy and safety of Ganaton (itopride hydrochloride) and mosapride citrate in the management of functional dyspepsiaJ Indian Med Assoc1027357PubMedGoogle Scholar
  132. 132.
    Seno, H, Nakase, H, Chiba, T 2005Usefulness of famotidine in functional dyspepsia patient treatment: comparison among prokinetic, acid suppression and antianxiety therapiesAliment Pharmacol Ther21326PubMedCrossRefGoogle Scholar
  133. 133.
    Otaka, M, Jin, M, Odashima, M, Matsuhashi, T, Wada, I, Horikawa, Y,  et al. 2005New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptylineAliment Pharmacol Ther21426PubMedCrossRefGoogle Scholar
  134. 134.
    Kinoshita, Y, Hashimoto, T, Kawamura, A, Yuki, M, Amano, K, Sato, H,  et al. 2005Effects of famotidine, mosapride and tandospirone for treatment of functional dyspepsiaAliment Pharmacol Ther213741PubMedCrossRefGoogle Scholar
  135. 135.
    Hongo, M 2006Initial approach and pharmacotherapy for functional dyspepsia—a large clinical trial in Japan (abstr)Gastroenterology130A-506Google Scholar
  136. 136.
    Katagiri, F, Shiga, T, Inoue, S, Sato, Y, Itoh, H, Takeyama, M 2006Effects of itopride hydrochloride on plasma gut-regulatory peptide and stress-related hormone levels in healthy human subjectsPharmacology7711521PubMedCrossRefGoogle Scholar
  137. 137.
    Holtmann, G, Talley, NJ, Liebregts, T, Adam, B, Parow, C 2006A placebo-controlled trial of itopride in functional dyspepsiaN Engl J Med35483240PubMedCrossRefGoogle Scholar
  138. 138.
    Feinle, C, Meier, O, Otto, B, D'Amato, M, Fried, M 2001Role of duodenal lipid and cholecystokinin A receptors in the pathophysiology of functional dyspepsiaGut4834755PubMedCrossRefGoogle Scholar
  139. 139.
    Galligan, JJ, Vanner, S 2005Basic and clinical pharmacology of new motility promoting agentsNeurogastroenterol Motil1764353PubMedCrossRefGoogle Scholar
  140. 140.
    Coffin, B, Bouhassira, D, Chollet, R, Fraitag, B, De Meynard, C, Geneve, J,  et al. 1996Effect of the kappa agonist fedotozine on perception of gastric distension in healthy humansAliment Pharmacol Ther1091925PubMedCrossRefGoogle Scholar
  141. 141.
    Read, NW, Abitbol, JL, Bardhan, KD, Whorwell, PJ, Fraitag, B 1997Efficacy and safety of the peripheral kappa agonist fedotozine versus placebo in the treatment of functional dyspepsiaGut416648PubMedCrossRefGoogle Scholar
  142. 142.
    Delgado-Aros, S, Chial, HJ, Cremonini, F, Ferber, I, McKinzie, S, Burton, DD,  et al. 2003Effects of asimadoline, a kappa-opioid agonist, on satiation and postprandial symptoms in healthAliment Pharmacol Ther1850714PubMedCrossRefGoogle Scholar
  143. 143.
    Fukuda, H, Suenaga, K, Tsuchida, D, Mantyh, CR, Pappas, TN, Hicks, GA,  et al. 2006The selective mu opioid receptor antagonist, alvimopan, improves delayed GI transit of postoperative ileus in ratsBrain Res11026370PubMedCrossRefGoogle Scholar
  144. 144.
    Sivarao, DV, Krowicki, ZK, Abrahams, TP, Hornby, PJ 1999Vagally-regulated gastric motor activity: evidence for kainate and NMDA receptor mediationEur J Pharmacol36817382PubMedCrossRefGoogle Scholar
  145. 145.
    Kuiken, SD, Lei, A, Tytgat, GN, Holman, R, Boeckxstaens, GE 2002Effect of the low-affinity, noncompetitive N-methyl-d-aspartate receptor antagonist dextromethorphan on visceral perception in healthy volunteersAliment Pharmacol Ther16195562PubMedCrossRefGoogle Scholar
  146. 146.
    Kuiken, SD, van den Berg, SJ, Tytgat, GN, Boeckxstaens, GE 2004Oral S(+)-ketamine does not change visceral perception in healthDig Dis Sci49174551PubMedCrossRefGoogle Scholar
  147. 147.
    Holzer, P, Holzer-Petsche, U 1997Tachykinins in the gut. Part II. Roles in neural excitation, secretion and inflammationPharmacol Ther7321963PubMedCrossRefGoogle Scholar
  148. 148.
    Sharma, R, Tobin, P, Clarke, SJ 2005Management of chemotherapy-induced nausea, vomiting, oral mucositis, and diarrhoeaLancet Oncol693102PubMedCrossRefGoogle Scholar
  149. 149.
    Monnikes, H, van der Voort, IR, Wollenberg, B, Heymann-Monnikes, I, Tebbe, JJ, Alt, W,  et al. 2005Gastric perception thresholds are low and sensory neuropeptide levels high in Helicobacter pylori-positive functional dyspepsiaDigestion7111123PubMedCrossRefGoogle Scholar
  150. 150.
    Fioramonti, J, Gaultier, E, Toulouse, M, Sanger, GJ, Bueno, L 2003Intestinal anti-nociceptive behaviour of NK3 receptor antagonism in conscious rats: evidence to support a peripheral mechanism of actionNeurogastroenterol Motil153639PubMedCrossRefGoogle Scholar
  151. 151.
    Kawabata, A 2003Gastrointestinal functions of proteinase-activated receptorsLife Sci7424754PubMedCrossRefGoogle Scholar
  152. 152.
    Kawabata, A, Kuroda, R, Nagata, N, Kawao, N, Masuko, T, Nishikawa, H,  et al. 2001In vivo evidence that protease-activated receptors 1 and 2 modulate gastrointestinal transit in the mouseBr J Pharmacol13312138PubMedCrossRefGoogle Scholar
  153. 153.
    Mule, F, Pizzuti, R, Capparelli, A, Vergnolle, N 2004Evidence for the presence of functional protease activated receptor 4 (PAR4) in the rat colonGut5322934PubMedCrossRefGoogle Scholar
  154. 154.
    Gilja, OH, Hausken, T, Bang, CJ, Berstad, A 1997Effect of glyceryl trinitrate on gastric accommodation and symptoms in functional dyspepsiaDig Dis Sci42212431PubMedCrossRefGoogle Scholar
  155. 155.
    Sarnelli, G, Sifrim, D, Janssens, J, Tack, J 2004Influence of sildenafil on gastric sensorimotor function in humansAm J Physiol Gastrointest Liver Physiol287G98892PubMedCrossRefGoogle Scholar
  156. 156.
    Tatsuta, M, Iishi, H 1993Effect of treatment with liu-jun-zi-tang (TJ-43) on gastric emptying and gastrointestinal symptoms in dyspeptic patientsAliment Pharmacol Ther745962PubMedCrossRefGoogle Scholar
  157. 157.
    Hayakawa, T, Arakawa, T, Kase, Y, Akiyama, S, Ishige, A, Takeda, S,  et al. 1999Liu-Jun-Zi-Tang, a kampo medicine, promotes adaptive relaxation in isolated guinea pig stomachsDrugs Exp Clin Res252118PubMedGoogle Scholar
  158. 158.
    Oikawa, T, Ito, G, Koyama, H, Hanawa, T 2005Prokinetic effect of a Kampo medicine, hange-koboku-to (banxia-houpo-tang), on patients with functional dyspepsiaPhytomedicine127304PubMedCrossRefGoogle Scholar
  159. 159.
    Hohenester, B, Ruhl, A, Kelber, O, Schemann, M 2004The herbal preparation STW5 (lberogast) has potent and region-specific effects on gastric motilityNeurogastroenterol Motil1676573PubMedCrossRefGoogle Scholar
  160. 160.
    Takahashi, T 2006Acupuncture for functional gastrointestinal disordersJ Gastroenterol4140817PubMedCrossRefGoogle Scholar
  161. 161.
    Park, MI, Camilleri, M 2006Gastroparesis: clinical updateAm J Gastroenterol101112939PubMedCrossRefGoogle Scholar
  162. 162.
    Monnikes, H, van der Voort, IR 2006Gastric electrical stimulation in gastroparesis: where do we stand?Dig Dis242606PubMedCrossRefGoogle Scholar
  163. 163.
    Sun, Y, Chen, JD 2005Gastric electrical stimulation reduces gastric tone energy dependentlyScand J Gastroenterol401549PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 2006

Authors and Affiliations

  • Yohei Mizuta
    • 1
  • Saburo Shikuwa
    • 1
  • Hajime Isomoto
    • 1
  • Ryosuke Mishima
    • 1
  • Yuko Akazawa
    • 1
  • Jun-ichi Masuda
    • 1
  • Katsuhisa Omagari
    • 1
  • Fuminao Takeshima
    • 2
  • Shigeru Kohno
    • 1
  1. 1.Second Department of Internal MedicineNagasaki University School of MedicineNagasakiJapan
  2. 2.Department of General MedicineNagasaki University School of MedicineNagasakiJapan

Personalised recommendations