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. 2004 Mar;53(Suppl 2):ii19–ii21. doi: 10.1136/gut.2003.033456

Putative therapeutic targets in the treatment of visceral hyperalgesia

S Collins
PMCID: PMC1867768  PMID: 14960554

Abstract

The management of abdominal pain remains a major challenge for clinicians despite an explosion of knowledge regarding the physiology and pathophysiology of sensory neural circuits. Initial progress was made in the field of somatic pain and this provided broad hypotheses that could be tested in the field of visceral pain. The major advances in our understanding of basic mechanisms underlying visceral pain originated in the urinary tract and have been applied to the gut. As yet, this increased understanding of enteric sensory physiology has yet to generate new effective treatments for abdominal pain. This review addresses novel insights into peripheral mechanisms underlying visceral hyperalgesia and their applicability to the development of novel therapeutic approaches to the treatment of chronic abdominal pain.

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Selected References

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  1. Accarino A. M., Azpiroz F., Malagelada J. R. Selective dysfunction of mechanosensitive intestinal afferents in irritable bowel syndrome. Gastroenterology. 1995 Mar;108(3):636–643. doi: 10.1016/0016-5085(95)90434-4. [DOI] [PubMed] [Google Scholar]
  2. Benham C. D., Davis J. B., Randall A. D. Vanilloid and TRP channels: a family of lipid-gated cation channels. Neuropharmacology. 2002 Jun;42(7):873–888. doi: 10.1016/s0028-3908(02)00047-3. [DOI] [PubMed] [Google Scholar]
  3. Bernstein C. N., Niazi N., Robert M., Mertz H., Kodner A., Munakata J., Naliboff B., Mayer E. A. Rectal afferent function in patients with inflammatory and functional intestinal disorders. Pain. 1996 Aug;66(2-3):151–161. doi: 10.1016/0304-3959(96)03062-x. [DOI] [PubMed] [Google Scholar]
  4. Chadwick Vinton S., Chen Wangxue, Shu Dairu, Paulus Barbara, Bethwaite Peter, Tie Andy, Wilson Ian. Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology. 2002 Jun;122(7):1778–1783. doi: 10.1053/gast.2002.33579. [DOI] [PubMed] [Google Scholar]
  5. Collins S. M., Piche T., Rampal P. The putative role of inflammation in the irritable bowel syndrome. Gut. 2001 Dec;49(6):743–745. doi: 10.1136/gut.49.6.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cook I. J., van Eeden A., Collins S. M. Patients with irritable bowel syndrome have greater pain tolerance than normal subjects. Gastroenterology. 1987 Oct;93(4):727–733. doi: 10.1016/0016-5085(87)90434-3. [DOI] [PubMed] [Google Scholar]
  7. Gunthorpe Martin J., Benham Christopher D., Randall Andrew, Davis John B. The diversity in the vanilloid (TRPV) receptor family of ion channels. Trends Pharmacol Sci. 2002 Apr;23(4):183–191. doi: 10.1016/s0165-6147(02)01999-5. [DOI] [PubMed] [Google Scholar]
  8. Hillsley K., Grundy D. Serotonin and cholecystokinin activate different populations of rat mesenteric vagal afferents. Neurosci Lett. 1998 Oct 16;255(2):63–66. doi: 10.1016/s0304-3940(98)00690-9. [DOI] [PubMed] [Google Scholar]
  9. Humphrey P. P., Bountra C., Clayton N., Kozlowski K. Review article: the therapeutic potential of 5-HT3 receptor antagonists in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther. 1999 May;13 (Suppl 2):31–38. [PubMed] [Google Scholar]
  10. Höfer Dirk, Asan Esther, Drenckhahn Detlev. Chemosensory Perception in the Gut. News Physiol Sci. 1999 Feb;14(NaN):18–23. doi: 10.1152/physiologyonline.1999.14.1.18. [DOI] [PubMed] [Google Scholar]
  11. Iversen Leslie, Chapman Victoria. Cannabinoids: a real prospect for pain relief? Curr Opin Pharmacol. 2002 Feb;2(1):50–55. doi: 10.1016/s1471-4892(01)00120-5. [DOI] [PubMed] [Google Scholar]
  12. Kerr B. J., Souslova V., McMahon S. B., Wood J. N. A role for the TTX-resistant sodium channel Nav 1.8 in NGF-induced hyperalgesia, but not neuropathic pain. Neuroreport. 2001 Oct 8;12(14):3077–3080. doi: 10.1097/00001756-200110080-00019. [DOI] [PubMed] [Google Scholar]
  13. Kirchgessner A. L., Tamir H., Gershon M. D. Identification and stimulation by serotonin of intrinsic sensory neurons of the submucosal plexus of the guinea pig gut: activity-induced expression of Fos immunoreactivity. J Neurosci. 1992 Jan;12(1):235–248. doi: 10.1523/JNEUROSCI.12-01-00235.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Krammer H. J., Kühnel W. Topography of the enteric nervous system in Peyer's patches of the porcine small intestine. Cell Tissue Res. 1993 May;272(2):267–272. doi: 10.1007/BF00302732. [DOI] [PubMed] [Google Scholar]
  15. Mayer E. A., Raybould H. E. Role of visceral afferent mechanisms in functional bowel disorders. Gastroenterology. 1990 Dec;99(6):1688–1704. doi: 10.1016/0016-5085(90)90475-g. [DOI] [PubMed] [Google Scholar]
  16. McMahon S. B. NGF as a mediator of inflammatory pain. Philos Trans R Soc Lond B Biol Sci. 1996 Mar 29;351(1338):431–440. doi: 10.1098/rstb.1996.0039. [DOI] [PubMed] [Google Scholar]
  17. Morrison L. A., Sidman R. L., Fields B. N. Direct spread of reovirus from the intestinal lumen to the central nervous system through vagal autonomic nerve fibers. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3852–3856. doi: 10.1073/pnas.88.9.3852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Naliboff B. D., Munakata J., Chang L., Mayer E. A. Toward a biobehavioral model of visceral hypersensitivity in irritable bowel syndrome. J Psychosom Res. 1998 Dec;45(6):485–492. doi: 10.1016/s0022-3999(98)00049-x. [DOI] [PubMed] [Google Scholar]
  19. Nobaek S., Johansson M. L., Molin G., Ahrné S., Jeppsson B. Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome. Am J Gastroenterol. 2000 May;95(5):1231–1238. doi: 10.1111/j.1572-0241.2000.02015.x. [DOI] [PubMed] [Google Scholar]
  20. O'Sullivan M., Clayton N., Breslin N. P., Harman I., Bountra C., McLaren A., O'Morain C. A. Increased mast cells in the irritable bowel syndrome. Neurogastroenterol Motil. 2000 Oct;12(5):449–457. doi: 10.1046/j.1365-2982.2000.00221.x. [DOI] [PubMed] [Google Scholar]
  21. Pimentel M., Chow E. J., Lin H. C. Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome. Am J Gastroenterol. 2000 Dec;95(12):3503–3506. doi: 10.1111/j.1572-0241.2000.03368.x. [DOI] [PubMed] [Google Scholar]
  22. Rodríguez L. A., Ruigómez A. Increased risk of irritable bowel syndrome after bacterial gastroenteritis: cohort study. BMJ. 1999 Feb 27;318(7183):565–566. doi: 10.1136/bmj.318.7183.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Silverman D. H., Munakata J. A., Ennes H., Mandelkern M. A., Hoh C. K., Mayer E. A. Regional cerebral activity in normal and pathological perception of visceral pain. Gastroenterology. 1997 Jan;112(1):64–72. doi: 10.1016/s0016-5085(97)70220-8. [DOI] [PubMed] [Google Scholar]
  24. Vergnolle N., Wallace J. L., Bunnett N. W., Hollenberg M. D. Protease-activated receptors in inflammation, neuronal signaling and pain. Trends Pharmacol Sci. 2001 Mar;22(3):146–152. doi: 10.1016/s0165-6147(00)01634-5. [DOI] [PubMed] [Google Scholar]
  25. Weston A. P., Biddle W. L., Bhatia P. S., Miner P. B., Jr Terminal ileal mucosal mast cells in irritable bowel syndrome. Dig Dis Sci. 1993 Sep;38(9):1590–1595. doi: 10.1007/BF01303164. [DOI] [PubMed] [Google Scholar]

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