Skip to main content
SpringerLink
Log in

Neuro-gastroenterology: Central and Autonomic Nervous System

  • Chapter
  • First Online:
Functional Dyspepsia

  • 444 Accesses

Abstract

The pathophysiology of functional dyspepsia (FD) is multifactorial. The Japanese clinical practice guideline for FD published in 2014 proposes two steps of pharmacological treatment strategy: initial treatment including acid suppressants or prokinetics (strong recommendation), and second-line treatment including anxiolytics, antidepressants, and Japanese traditional medicine (weak recommendation). However, the definitive treatment flow has not been established.

Recently, accumulating lines of evidence indicate that FD patients experience visceral hypersensitivity as one of the functional disorders of the gastrointestinal tract. In other words, abdominal symptoms are caused by mild chemical (gastric acid) and mechanical (intraluminal distension) stimuli to the gastrointestinal tract on the basis of visceral hypersensitivity. Altered processing of visceral sensation from gastrointestinal tracts may also arise in the central nervous system (CNS) of FD patients. In addition, various gastrointestinal functions are regulated via the autonomic nervous system (ANS) throughout the interaction between the CNS and the enteric nervous system (ENS). All these findings suggest that the entire neuronal system is significantly involved in the pathogenesis of FD. This part will give the information about the neuro-gastroenterological interests of the pathophysiology of FD particularly for the CNS and the ANS.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Miwa H, Kusano M, Arisawa T, et al. Evidence-based clinical practice guidelines for functional dyspepsia. J Gastroenterol. 2015;50(2):125–39.

    Article  CAS  PubMed  Google Scholar 

  2. Iwakiri R, Tominaga K, Furuta K, Inamori M, Furuta T, Masuyama H, et al. Randomised clinical trial: rabeprazole improves symptoms in patients with functional dyspepsia in Japan. Aliment Pharmacol Ther. 2013;38:729–40.

    Article  CAS  PubMed  Google Scholar 

  3. Matsueda K, Hongo M, Tack J, Saito Y, Kato H. A placebo-controlled trial of acotiamide for meal-related symptoms of functional dyspepsia. Gut. 2012;61:821–8.

    Article  CAS  PubMed  Google Scholar 

  4. Miwa H, Nagahara A, Tominaga K, Yokoyama T, Sawada Y, Inoue K, et al. Efficacy of the 5-HT1A agonist tandospirone citrate in improving symptoms of patients with functional dyspepsia: a randomized controlled trial. Am J Gastroenterol. 2009;104:2779–87.

    Article  CAS  PubMed  Google Scholar 

  5. Suzuki H, Matsuzaki J, Fukushima Y, Suzaki F, Kasugai K, Nishizawa T, et al. Randomized clinical trial: rikkunshito in the treatment of functional dyspepsia-a multicenter, double-blind, randomized, placebo-controlled study. Neurogastroenterol Motil. 2014;26(7):950–61.

    Article  CAS  PubMed  Google Scholar 

  6. Carbone F, Tack J. Gastroduodenal mechanisms underlying functional gastric disorders. Dig Dis. 2014;32(3):222–9.

    Article  CAS  PubMed  Google Scholar 

  7. Ochi M, Tominaga K, Iketani T, Kadouchi K, Tanigawa T, Shiba M, et al. Perfectionism underlying psychological background correlated with the symptoms of functional dyspepsia. J Gastroenterol. 2008;43:699–704.

    Article  PubMed  Google Scholar 

  8. Tominaga K, Higuchi K, Iketani T, Ochi M, Kadouchi K, Tanigawa T, et al. Comparison of gastrointestinal symptoms and psychological factors of functional dyspepsia to peptic ulcer or panic disorders patients. Inflammopharmacology. 2007;15:84–9.

    Article  CAS  PubMed  Google Scholar 

  9. Oshima T, Okugawa T, Tomita T, Sakurai J, Toyoshima F, Watari J, 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(1):175–82.

    Article  CAS  PubMed  Google Scholar 

  10. Tominaga K, Fujikawa Y, Tsumoto C, Kadouchi K, Tanaka F, Kamata N, et al. Disorder of autonomic nervous system and its vulnerability to external stimulation in functional dyspepsia. J Clin Biochem Nutr. 2016;58(2):161–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tominaga K, Higuchi K, Ochi M, Kadouchi K, Kawamura E, Tanigawa T, et al. Concurrent assessment of reservoir and emptying of the stomach for dyspepsia patients. Hepato-Gastroenterology. 2008;55:744–9.

    PubMed  Google Scholar 

  12. Schuligoi R, Joci M, Heinemann A. Scho¨ninkle E, Pabst MA, Holzer P. Gastric acid–evoked c-fos messenger RNA expression in rat brainstem is signaled by capsaicin-resistant vagal afferents. Gastroenterology. 1998;115:649–60.

    Article  CAS  PubMed  Google Scholar 

  13. Lamb K, Kang YM, Gebhart GF, Bielefeldt K. Gastric inflammation triggers hypersensitivity to acid in awake rats. Gastroenterology. 2003;125(5):1410–8.

    Article  PubMed  Google Scholar 

  14. Miwa H, Nakajima K, Yamaguchi K, Fujimoto K, Veldhuyzen VAN Zanten SJ, et al. Generation of dyspeptic symptoms by direct acid infusion into the stomach of healthy Japanese subjects. Aliment Pharmacol Ther. 2007;26(2):257–64.

    Article  CAS  PubMed  Google Scholar 

  15. Holzer P, Painsipp E, Schuligoi R. Differential effects of intragastric acid and capsaicin on gastric emptying and afferent input to the rat spinal cord and brainstem. BMC Neurosci. 2005;6:60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lee KJ, Demarchi B, Demedts I, Sifrim D, Raeymaekers P, Tack J. A pilot study on duodenal acid exposure and its relationship to symptoms in functional dyspepsia with prominent nausea. Am J Gastroenterol. 2004;99(9):1765–73.

    Article  PubMed  Google Scholar 

  17. Sarnelli G, Caenepeel P, Geypens B, Janssens J, Tack J. Symptoms associated with impaired gastric emptying of solids and liquids in functional dyspepsia. Am J Gastroenterol. 2003;98(4):783–8.

    Article  PubMed  Google Scholar 

  18. Ladabaum U, Minoshima S, Hasler WL, Cross D, Chey WD, Owyang C. Gastric distention correlates with activation of multiple cortical and subcortical regions. Gastroenterology. 2001;120(2):369–76.

    Article  CAS  PubMed  Google Scholar 

  19. Blackshaw LA, Brierley SM, Hughes PA. TRP channels: new targets for visceral pain. Gut. 2010;59(1):126–35.

    Article  CAS  PubMed  Google Scholar 

  20. Vandenbergh J, Dupont P, Fischler B, Bormans G, Persoons P, Janssens J, et al. Regional brain activation during proximal stomach distention in humans: a positron emission tomography study. Gastroenterology. 2005;128:564–73.

    Article  PubMed  Google Scholar 

  21. Mertz H, Morgan V, Tanner G, Pickens D, Price R, Shyr Y, et al. Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention. Gastroenterology. 2000;118:842–8.

    Article  CAS  PubMed  Google Scholar 

  22. Drossman DA, Ringel Y, Vogt BA, Leserman J, Lin W, Smith JK, et al. Alterations of brain activity associated with resolution of emotional distress and pain in a case of severe irritable bowel syndrome. Gastroenterology. 2003;124:754–61.

    Article  PubMed  Google Scholar 

  23. Mearin F, Cucala M, Azpiroz F, Malagelada JR. The origin of symptoms on the brain-gut axis in functional dyspepsia. Gastroenterology. 1991;101:999–1006.

    Article  CAS  PubMed  Google Scholar 

  24. Van Oudenhove L, Vandenberghe J, Dupont P, Geeraerts B, Vos R, Dirix S, et al. Abnormal regional brain activity during rest and (anticipated) gastric distension in functional dyspepsia and the role of anxiety: a H(2)(15)O-PET study. Am J Gastroenterol. 2010;105:913–24.

    Article  PubMed  Google Scholar 

  25. Zeng F, Qin W, Liang F, Liu J, Tang Y, Liu X, et al. Abnormal resting brain activity in patients with functional dyspepsia is related to symptom severity. Gastroenterology. 2011;141:499–506.

    Article  PubMed  Google Scholar 

  26. Chen JJ, Li Z, Pan H, Murphy DL, Tamir H, Koepsell H, et al. Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter: June 2004 SEROTONIN AND UC/IBS 1663 abnormal intestinal motility and the expression of cation transporters. J Neurosci. 2001;21:6348–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wade PR, Chen J, Jaffe B, Kassem IS, Blakely RD, Gershon MD. Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract. J Neurosci. 1996;16:2352–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ichimiya T, Suhara T, Sudo Y, Okubo Y, Nakayama K, Nankai M, et al. Serotonin transporter binding in patients with mood disorders: a PET study with [11C](+)McN5652. Biol Psychiatry. 2002;51:715–22.

    Article  CAS  PubMed  Google Scholar 

  29. Cannon DM, Ichise M, Fromm SJ, Nugent AC, Rollis D, Gandhi SK, et al. Serotonin transporter binding in bipolar disorder assessed using [11C]DASB and positron emission tomography. Biol Psychiatry. 2006;60:207–17.

    Article  CAS  PubMed  Google Scholar 

  30. Tominaga K, Tsumoto C, Ataka S, Mizuno K, Takahashi K, Yamagami H, et al. Regional brain disorders of serotonin neurotransmission are associated with functional dyspepsia. Life Sci. 2015;137:150–7.

    Article  CAS  PubMed  Google Scholar 

  31. Grothe DR, Scheckener B, Albano D. Treatment of pain syndromes with venlafaxine. Pharmacotherapy. 2004;24:621–9.

    Article  CAS  PubMed  Google Scholar 

  32. Whitehead WE, Palsson OS. Is rectal pain sensitivity a biological marker for irritable bowel syndrome: psychological influences on pain perception. Gastroenterology. 1998;115:1263–71.

    Article  CAS  PubMed  Google Scholar 

  33. CL L, Wu YT, Yeh TC, Chen LF, Chang FY, Lee SD, et al. Neuronal correlates of gastric pain induced by fundus distension: a 3T-fMRI study. Neurogastroenterol Motil. 2004;16:575–87.

    Article  Google Scholar 

  34. Goyal RK, Hirano I. The enteric nervous system. N Engl J Med. 1996;334:1106–15.

    Article  CAS  PubMed  Google Scholar 

  35. Takahashi T, Owyang C. Characterization of vagal pathways mediating gastric accommodation reflex in rats. J Physiol. 1997;504:479–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Asakawa A, Inui A, Kaga T, Yuzuriha H, Nagata T, Ueno N, et al. Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology. 2001;120:337–45.

    Article  CAS  PubMed  Google Scholar 

  37. Raybould HE, Taché Y. Cholecystokinin inhibits gastric motility and emptying via a capsaicin-sensitive vagal pathway in rats. Am J Phys. 1988;255:G242–6.

    CAS  Google Scholar 

  38. Mayer EA, Aziz Q, Coen S, Kern M, Labus JS. Lane ret al. Brain imaging approaches to the study of functional GI disorders: a Rome working team report. Neurogastroenterol Motil. 2009;21:579–96.

    Article  CAS  PubMed  Google Scholar 

  39. Mayer EA, Naliboff BD, Chang L, Coutinho SV. V. Stress and irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2001;280:G519–24.

    Article  CAS  PubMed  Google Scholar 

  40. Sagami Y, Shimada Y, Tayama J, Nomura T, Satake M, Endo Y, et al. Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome. Gut. 2004;53:958–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Manabe N, Nakamura K, Hara M, Imamura H, Kusunoki H, Tanaka S, et al. Impaired gastric response to modified sham feeding in patients with postprandial distress syndrome. Neurogastroenterol Motil. 2011;23(3):215–9.

    Article  CAS  PubMed  Google Scholar 

  43. Larauche M, Mulak A, Taché Y. Stress and visceral pain: from animal models to clinical therapies. Exp Neurol. 2012;233(1):49–67.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Premier Developmental Research of Medicine, Osaka Medical College, Takatsuki, Osaka, Japan

    Kazunari Tominaga & Yoshiko Fujikawa

Authors
  1. Kazunari Tominaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshiko Fujikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kazunari Tominaga .

Editor information

Editors and Affiliations

  1. Premier Developmental Research of Medicine, Osaka Medical College, Takatsuki, Osaka, Japan

    Kazunari Tominaga

  2. Department of General Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan

    Hiroaki Kusunoki

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Tominaga, K., Fujikawa, Y. (2018). Neuro-gastroenterology: Central and Autonomic Nervous System. In: Tominaga, K., Kusunoki, H. (eds) Functional Dyspepsia. Springer, Singapore. https://doi.org/10.1007/978-981-13-1074-4_4

Download citation

  • DOI: https://doi.org/10.1007/978-981-13-1074-4_4

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-13-1073-7

  • Online ISBN: 978-981-13-1074-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation