A Rat Model of Chronic Postinflammatory Visceral Pain Induced by Deoxycholic Acid

Traub, Richard J.; Tang, Bin; Ji, Yaping; Pandya, S.M.; Yfantis, Harris G.; Sun, Ying

doi:10.1053/j.gastro.2008.08.051

Cited by 70 publications

(68 citation statements)

References 50 publications

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“…Given the irritant actions of BAs and the finding that repeated administration of high concentrations of DCA (4 mM) can cause colonic inflammation 37 , we examined whether the highest concentration of DCA (100 μΜ) induced damage to the colonic mucosa. Exposure of the mucosa of the isolated colon to 100 μΜ DCA for 10 min caused no detectable histological damage or neutrophil infiltration to the mucosa (Supporting Information Fig.…”

Section: Resultsmentioning

confidence: 99%

The Receptor TGR5 Mediates the Prokinetic Actions of Intestinal Bile Acids and Is Required for Normal Defecation in Mice

et al. 2013

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Background & Aims: Abnormal delivery of bile acids (BAs) to the colon, due to disease or therapy, causes constipation or diarrhea by unknown mechanisms. The G protein-coupled BA receptor TGR5 (or GPBAR1) is expressed by enteric neurons and endocrine cells, which regulate motility and secretion. Methods: We analyzed gastrointestinal and colon transit, and defecation frequency and water content, in wild-type, knockout and transgenic mice (trg5-wt, tgr5-ko and tgr5-tg, respectively). We analyzed colon tissues for contractility, peristalsis, and transmitter release. Results: Deoxycholic acid inhibited contractility of colonic longitudinal muscle from tgr5-wt but not tgr5-ko mice. Application of deoxycholic acid, lithocholic acid, or oleanolic acid (a selective agonist of TGR5) to the mucosa of tgr5-wt mice caused oral contraction and caudal relaxation, indicating peristalsis. BAs stimulated release of the peristaltic transmitters 5-hydroxytryptamine and calcitonin gene-related peptide; antagonists of these transmitters suppressed BA-induced peristalsis, consistent with TGR5 localization to enterochromaffin cells and intrinsic primary afferent neurons. tgr5-ko mice did not undergo peristalsis or transmitter release in response to BAs. Mechanically induced peristalsis and transmitter release were not affected by deletion of tgr5. Whole-gut transit was 1.4-fold slower in tgr5-ko than tgr5-wt or tgr5-tg mice, whereas colonic transit was 2.2-fold faster in tgr5-tg mice. Defecation frequency was reduced 2.6-fold in tgr5-ko and increased 1.4-fold in tgr5-tg mice, compared to tgr5-wt mice. Water content in stool was lower (37%) in tgr5-ko than tgr5-tg (58%) or tgr5-wt mice (62%). Conclusions: The receptor TGR5 mediates the effects of BAs on colonic motility; TGR5 deficiency causes constipation in mice. These findings might mediate the long-known laxative properties of BAs; TGR5 might be a therapeutic target for digestive diseases.

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Section: Resultsmentioning

confidence: 99%

The Receptor TGR5 Mediates the Prokinetic Actions of Intestinal Bile Acids and Is Required for Normal Defecation in Mice

et al. 2013

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“…Other approaches selectively directed at the colorectum include intracolonic treatment with inflamogens or irritants such as acetic acid, acidified hypertonic saline, trinitrobenzene sulfonic acid (TNBS), zymosan, deoxycholic acid (DCA), etc., or oral ingestion of dextran sodium sulfate (5 %) (e.g., Jones 2007;Traub et al 2008;La et al 2012;Feng et al 2012;Low et al 2013). Models of mild to severe colitis, hypersensitivity in the absence of inflammation, or post-inflammatory colitis have been described.…”

Section: Colorectal Distensionmentioning

confidence: 99%

Visceral Pain

Schwartz¹,

Gebhart²

2014

Current Topics in Behavioral Neurosciences

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Modeling visceral pain requires an appreciation of the underlying neurobiology of visceral sensation, including characteristics of visceral pain that distinguish it from pain arising from other tissues, the unique sensory innervation of visceral organs, the functional basis of visceral pain, and the concept of viscero-somatic and viscero-visceral convergence. Further, stimuli that are noxious when applied to the viscera are different than stimuli noxious to skin, muscle, and joints, thus informing model development and assessment. Visceral pain remains an important and understudied area of pain research and basic science knowledge and mechanisms acquired using animal models can translate into approaches that can be applied to the study and development of future therapeutics.

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“…51 Chemically induced mild, transient colitis results in persistent visceral hyperalgesia and referred pain in rats. 52 Evidence from animal studies suggests that chemically induced colitis and repeated colorectal distention in neonatal mice leads to chronic visceral hypersensitivity associated with peripheral and central sensitization as adults. The same phenomenon is not present if the noxious stimulus is applied in adulthood.…”

Section: Effects Of Exposure To Pain During the Neonatal Periodmentioning

confidence: 99%

Early life events predispose the onset of childhood functional gastrointestinal disorders

Bonilla

Saps

2013

Revista de Gastroenterología de México

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A Rat Model of Chronic Postinflammatory Visceral Pain Induced by Deoxycholic Acid

Cited by 70 publications

References 50 publications

The Receptor TGR5 Mediates the Prokinetic Actions of Intestinal Bile Acids and Is Required for Normal Defecation in Mice

The Receptor TGR5 Mediates the Prokinetic Actions of Intestinal Bile Acids and Is Required for Normal Defecation in Mice

Visceral Pain

Early life events predispose the onset of childhood functional gastrointestinal disorders

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