Pathophysiology Underlying the Irritable Bowel Syndrome

Wood, Jackie D.

doi:10.1016/b978-0-12-382026-6.00081-6

Cited by 4 publications

(1 citation statement)

References 189 publications

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“…A disordered enteric nervous system (ENS) might underlie some forms of IBS pathophysiology 7,8. Activity of the musculature, glands and vascular system to generate functionally effective patterns of behavior, which are adaptive for differing digestive states, is controlled by the ENS.…”

Section: Introductionmentioning

confidence: 99%

Anti-Enteric Neuronal Antibodies and the Irritable Bowel Syndrome

Wood¹,

Liu²,

Drossman³

et al. 2012

J Neurogastroenterol Motil

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Background/AimsFunctional gastrointestinal disorders are those in which no abnormal metabolic or physical processes, which can account for the symptoms, can be identified. The irritable bowel syndrome (IBS) is a significant functional disorder, which affects 10-20 percent of the population worldwide. Predominant symptoms of IBS are abnormal defecation associated with abdominal pain, both of which may be exacerbated by psychogenic stress. Our study was designed to test a hypothesis that symptoms in a subset of patients with a diagnosis of IBS are associated with an autoimmune degenerative neuropathy in the enteric nervous system.MethodsSerum was collected from Rome II-IBS patients and controls at the University of North Carolina Functional Gastrointestinal Diseases Center. Assay procedures were immunohistochemical localization of antibody binding to enteric neurons and human protein microarray assay for antigens recognized by antibodies in the sera.ResultsEighty-seven percent of IBS sera and 59% of control sera contained anti-enteric neuronal antibodies. Antibody immunostaining was seen in the nucleus and cytoplasm of neurons in the enteric nervous system. Protein microarray analysis detected antibody reactivity for autoantigens in serum with anti-enteric neuronal antibodies and no reactivity for the same autoantigens in samples not containing anti-enteric neuronal antibodies in our immunostaining assay. Antibodies in sera from IBS patients recognized only 3 antigens out of an 8,000 immunoprotein array. The 3 antigens were: (1) a nondescript ribonucleoprotein (RNP-complex); (2) small nuclear ribonuclear polypeptide A; and (3) Ro-5,200 kDa.ConclusionsResults of the present study suggest that symptoms in a subset of IBS patients might be a reflection of enteric neuronal damage or loss, caused by circulating anti-enteric autoimmune antibodies.

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Section: Introductionmentioning

confidence: 99%

Anti-Enteric Neuronal Antibodies and the Irritable Bowel Syndrome

Wood¹,

Liu²,

Drossman³

et al. 2012

J Neurogastroenterol Motil

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The enteric purinergic P2Y1 receptor

Wood

2006

Current Opinion in Pharmacology

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Innervation of enteric mast cells by primary spinal afferents in guinea pig and human small intestine

Wang

Liu

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Mast cells express the substance P (SP) neurokinin 1 receptor and the calcitonin gene-related peptide (CGRP) receptor in guinea pig and human small intestine. Enzyme-linked immunoassay showed that activation of intramural afferents by antidromic electrical stimulation or by capsaicin released SP and CGRP from human and guinea pig intestinal segments. Electrical stimulation of the afferents evoked slow excitatory postsynaptic potentials (EPSPs) in the enteric nervous system. The slow EPSPs were mediated by tachykinin neurokinin 1 and CGRP receptors. Capsaicin evoked slow EPSP-like responses that were suppressed by antagonists for protease-activated receptor 2. Afferent stimulation evoked slow EPSP-like excitation that was suppressed by mast cell-stabilizing drugs. Histamine and mast cell protease II were released by 1) exposure to SP or CGRP, 2) capsaicin, 3) compound 48/80, 4) elevation of mast cell Ca²⁺ by ionophore A23187, and 5) antidromic electrical stimulation of afferents. The mast cell stabilizers cromolyn and doxantrazole suppressed release of protease II and histamine when evoked by SP, CGRP, capsaicin, A23187, electrical stimulation of afferents, or compound 48/80. Neural blockade by tetrodotoxin prevented mast cell protease II release in response to antidromic electrical stimulation of mesenteric afferents. The results support a hypothesis that afferent innervation of enteric mast cells releases histamine and mast cell protease II, both of which are known to act in a diffuse paracrine manner to influence the behavior of enteric nervous system neurons and to elevate the sensitivity of spinal afferent terminals.

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Pathophysiology Underlying the Irritable Bowel Syndrome

Cited by 4 publications

References 189 publications

Anti-Enteric Neuronal Antibodies and the Irritable Bowel Syndrome

Anti-Enteric Neuronal Antibodies and the Irritable Bowel Syndrome

The enteric purinergic P2Y1 receptor

Innervation of enteric mast cells by primary spinal afferents in guinea pig and human small intestine

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