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Luminal Stimuli Acutely Sensitize Visceromotor Responses to Distension of the Rat Stomach

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Abstract

Inflammation can enhance responses to different stimuli consistent with the development of hypersensitivity. To determine whether sequentially applied stimuli interact, we determined visceromotor responses (VMR) to gastric distension, measured at baseline and 60 min after instillation of saline, glycocholic acid (GCA) or ethanol through a gastrostomy in controls and rats with gastric ulcers. In another series of experiments, chemicals were administered before and 60 min after repeated distension of the stomach. Ethanol, but not saline or GCA, increased VMR in controls with a more significant rise in rats with gastric ulcerations. GCA increased responses to gastric distension in controls, whereas GCA and ethanol enhanced responses to gastric distensions in rats with gastric ulcers. Responses to saline, GCA, or ethanol were not affected by repeated noxious distension of the stomach. Luminal stimuli can trigger visceromotor responses and sensitize gastric afferents to mechanical stimulation, thus potentially contributing to dyspeptic symptoms.

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References

  1. Agreus L, Talley NJ (1998) Dyspepsia: current understanding and management. Annu Rev Med 49:475–493

    Article  PubMed  CAS  Google Scholar 

  2. Bouin M, Meunier P, Riberdy-Poitras M, et al (2001) Pain hypersensitivity in patients with functional gastrointestinal disorders: a gastrointestinal-specific defect or a general systemic condition? Dig Dis Sci 46:2542–2548

    Article  PubMed  CAS  Google Scholar 

  3. Tack J, Caenepeel P, Fischler B, et al (2001) Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia. Gastroenterology 121:526–535

    Article  PubMed  CAS  Google Scholar 

  4. Fass R, Naliboff B, Higa L, et al (1998) Differential effect of long-term esophageal acid exposure on mechanosensitivity and chemosensitivity in humans. Gastroenterology 115:1363–1373

    Article  PubMed  Google Scholar 

  5. George AA, Tsuchiyose M, Dooley CP (1991) Sensitivity of the gastric mucosa to acid and duodenal contents in patients with nonulcer dyspepsia. Gastroenterology 101:3–6

    PubMed  CAS  Google Scholar 

  6. Kern M, Hofmann C, Hyde J, et al (2004) Characterization of the cerebral cortical representation of heartburn in GERD patients. Am J Physiol 286:G174–G181

    CAS  Google Scholar 

  7. Coffin B, Chollet R, Flourie B, et al (2001) Intraluminal modulation of gastric sensitivity to distension: Effects of hydrochloric acid and meal. Am J Physiol 280:G904–G909

    CAS  Google Scholar 

  8. Hu WHC, Martin CJ, Talley NJ (2000) Intraesophageal acid perfusion sensitizes the esophagus to mechanical distension: A barostat study. Am J Gastroenterol 95:2189–2194

    Article  PubMed  CAS  Google Scholar 

  9. Lamb K, Kang YM, Gebhart GF, et al (2003) Gastric inflammation triggers hypersensitivity to acid in awake rats. Gastroenterology 125:1410–1418

    Article  PubMed  Google Scholar 

  10. Kang YM, Bielefeldt K, Gebhart GF (2004) Sensitization of mechanosensitive gastric vagal afferent fibers in the rat by thermal and chemical stimuli and gastric ulcers. J Neurophysiol 91:1981–1989

    Article  PubMed  CAS  Google Scholar 

  11. Ozaki N, Gebhart GF (2001) Characterization of mechanosensitive splanchnic nerve afferent fibers innervating the rat stomach. Am J Physiol 281:G1449–G1459

    CAS  Google Scholar 

  12. Sibilia V, Rindi G, Pagani F, et al (2003) Ghrelin protects against ethanol-induced gastric ulcers in rats: Studies on the mechanisms of action. Endocrinology 144:353–359

    Article  PubMed  CAS  Google Scholar 

  13. Kang YM, Lamb K, Gebhart GF, et al (2005) Experimentally induced ulcers and gastric sensory-motor function in rats. Am J Physiol 288:G284–G291

    CAS  Google Scholar 

  14. Lamb K, Kang YM, Gebhart GF, et al (2003) Nerve growth factor and gastric hyperalgesia in the rat. Neurogastroenterol Motil 15:355–361

    Article  PubMed  CAS  Google Scholar 

  15. Ozaki N, Bielefeldt K, Sengupta JN, et al (2002) Models of gastric hyperalgesia in the rat. Am J Physiol 283:G666–G676

    CAS  Google Scholar 

  16. Mearin F, De Ribot X, Balboa A, et al (1995) Duodenogastric bile reflux and gastrointestinal motility in pathogenesis of functional dyspepsia. Role of cholecystectomy. Dig Dis Sci 40:1703–1709

    Article  PubMed  CAS  Google Scholar 

  17. Sun Y, Fihn BM, Sjovall H, et al (2004) Enteric neurones modulate the colonic permeability response to luminal bile acids in rat colon in vivo. Gut 53:362–367

    Article  PubMed  CAS  Google Scholar 

  18. Ma TY, Nguyen D, Bui V, et al (1999) Ethanol modulation of intestinal epithelial tight junction barrier. Am J Physiol 276:G965–G974

    PubMed  CAS  Google Scholar 

  19. Faingold CL, N’gouemo P, Riaz A (1998) Ethanol and neurotransmitter interactions: from molecular to integrative effects. Prog Neurobiol 55:509–535

    Article  PubMed  CAS  Google Scholar 

  20. Gruss M, Henrich M, Konig P, et al (2001) Ethanol reduces excitability in a subgroup of primary sensory neurons by activation of bKCa channels. Eur J Neurosci 14:1246–1256

    Article  PubMed  CAS  Google Scholar 

  21. Fink K, Gothert M (1996) Both ethanol and ifenprodil inhibit nmda-evoked release of various neurotransmitters at different, yet proportional potency: Potential relation to nmda receptor subunit composition. Naunyn Schmiedebergs Arch Pharmacol 354:312–319

    Article  PubMed  CAS  Google Scholar 

  22. Kamp EH, Jones RCW, Tillman SR, et al (2003) Quantitative assessment and characterization of visceral nociception and hyperalgesia in mice. Am J Physiol 284:G434–444

    CAS  Google Scholar 

  23. Ness TJ, Gebhart GF (1988) Colorectal distension as a noxious visceral stimulus: Physiologic and pharmacologic characterization of pseudaffective reflexes in the rat. Brain Res 450:153–169

    Article  PubMed  CAS  Google Scholar 

  24. Munakata J, Naliboff B, Harraf F, et al (1997) Repetitive sigmoid stimulation induces rectal hyperalgesia in patients with irritable bowel syndrome. Gastroenterology 112:55–63

    Article  PubMed  CAS  Google Scholar 

  25. Gschossmann JM, Coutinho SV, Miller JC, et al (2001) Involvement of spinal calcitonin gene-related peptide in the development of acute visceral hyperalgesia in the rat. Neurogastroenterol Motil 13:229–236

    Article  PubMed  CAS  Google Scholar 

  26. Million M, Wang L, Wang Y, et al (2006) CRF2 receptor activation prevents colorectal distension induced visceral pain and spinal ERK1/2 phosphorylation in rats. Gut 55:172–181

    Article  PubMed  CAS  Google Scholar 

  27. Page AJ, Martin CM, Blackshaw LA (2002) Vagal mechanoreceptors and chemoreceptors in mouse stomach and esophagus. J Neurophysiol 87:2095–2103

    PubMed  CAS  Google Scholar 

  28. Berthoud HR, Lynn PA, Blackshaw LA (2001) Vagal and spinal mechanosensors in the rat stomach and colon have multiple receptive fields. Am J Physiol 280:R1371–R1381

    CAS  Google Scholar 

  29. Page AJ, Blackshaw LA (1998) An in vitro study of the properties of vagal afferent fibres innervating the ferret oesophagus and stomach. J Physiol (Lond) 512:907–916

    Article  CAS  Google Scholar 

  30. Gebhart GF (2000) Pathobiology of visceral pain: Molecular mechanisms and therapeutic implications IV. Visceral afferent contributions to the pathobiology of visceral pain. Am J Physiol 278:G834–G838

    CAS  Google Scholar 

  31. Mayer EA (2000) Spinal and supraspinal modulation of visceral sensation. Gut 47(Suppl 4):69–72

    Google Scholar 

  32. Bielefeldt K, Ozaki N, Gebhart GF (2002) Experimental ulcers alter voltage-sensitive sodium currents in rat gastric sensory neurons. Gastroenterology 122:394–405

    Article  PubMed  CAS  Google Scholar 

  33. Dang K, Bielefeldt K, Gebhart GF (2004) Modulation of potassium currents in a model of gastric hyperalgesia. Am J Physiol 286:G573–G579

    Article  CAS  Google Scholar 

  34. Tack J, Demedts I, Dehondt G, et al (2002) Clinical and pathophysiological characteristics of acute-onset functional dyspepsia. Gastroenterology 122:1738–1747

    Article  PubMed  Google Scholar 

  35. Spiller RC (2003) Postinfectious irritable bowel syndrome. Gastroenterology 124:1662–1671

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, University of Iowa, Iowa City, Iowa, USA

    K. Lamb & G. F. Gebhart

  2. Department of Anesthesiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    G. F. Gebhart

  3. Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    K. Bielefeldt

  4. Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    G. F. Gebhart

  5. Division of Gastroenterology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA, 15213, USA

    K. Bielefeldt

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  1. K. Lamb
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  2. G. F. Gebhart
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  3. K. Bielefeldt
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Correspondence to K. Bielefeldt.

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Supported by a grant from the National Institutes of Health (NS 35790).

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Lamb, K., Gebhart, G.F. & Bielefeldt, K. Luminal Stimuli Acutely Sensitize Visceromotor Responses to Distension of the Rat Stomach. Dig Dis Sci 52, 488–494 (2007). https://doi.org/10.1007/s10620-006-9621-3

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  • DOI: https://doi.org/10.1007/s10620-006-9621-3

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