Gastroenterology

Gastroenterology

Volume 119, Issue 5, November 2000, Pages 1276-1285
Gastroenterology

Alimentary Tract
A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development

https://doi.org/10.1053/gast.2000.19576Get rights and content

Abstract

Background & Aims The irritable bowel syndrome (IBS) is a common disorder characterized by abdominal pain in the setting of altered perception of viscerosensory stimuli. This so-called visceral hyperalgesia occurs in the absence of detectable organic disease in the peripheral organs and may cause normal or physiologic contractions to be perceived as painful. Although the pathogenesis of IBS remains speculative and is probably multifactorial, a prevailing paradigm is that transient noxious events lead to long-lasting sensitization of the neural pain circuit, despite complete resolution of the initiating event. Methods Neonatal male Sprague–Dawley rats received either mechanical or chemical colonic irritation between postnatal days 8 and 21 and were tested when they became adults. The abdominal withdrawal reflex and the responses of viscerosensitive neurons were recorded during colon distention. Results Colon irritation in neonates, but not in adults, results in chronic visceral hypersensitivity, with characteristics of allodynia and hyperalgesia, associated with central neuronal sensitization in the absence of identifiable peripheral pathology. Conclusions These results concur largely with observations in patients with IBS, providing a new animal model to study IBS and validating a neurogenic component of functional abdominal pain that encourages novel approaches to health care and research.

GASTROENTEROLOGY 2000;119:1276-1285

Section snippets

Animals

Experiments were performed using male Sprague–Dawley rats obtained as preweanling neonates (younger than 8 days) from Harlan Sprague–Dawley Inc. (Indianapolis, IN). Rats were housed in plastic cages containing corn chip bedding (Sani-Chips; PJ Murphy Forest Products, Montville, NJ) and maintained on a 12:12-hour light-dark cycle (lights on at 7 AM). The irritation procedure and the experimental testing were conducted during the light component of the cycle. The neonates were housed 12 in a cage

Results

CI in neonatal rats leads to a state of chronic visceral hypersensitivity in adults manifested by increased contractility of abdominal muscles and hyperexcitability of viscerosensitive neurons in the lumbosacral cord. This hypersensitivity occurs in the absence of identifiable histopathology in the adult colon and does not alter the growth rate of the rats with CI. In fact, sections from the colons of 12 rats (4 with neonatal CRD, 4 with neonatal mustard oil treatment, and 4 controls) were

Discussion

Pain is a central feature in the lives of patients with IBS; in the more severe cases, it can be prominent enough to give rise to the term “pain career.”10 The lack of overt visceral pathology, along with reported associations with childhood sexual, physical, and verbal abuse, has resulted in several psychologic hypotheses to explain this so-called functional abdominal pain.6 Alternatively, such pain may be the result of sensitization of the nervous system at a vulnerable state in its

Acknowledgements

The authors thank Dr. Shu-Yuan Xiao, Department of Pathology, University of Texas Medical Branch, for his expert evaluation of the colonic tissues.

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    Address requests for reprints to: Elie D. Al-Chaer, Ph.D., Departments of Internal Medicine and Anatomy and Neurosciences, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555-0632. e-mail: [email protected]; fax: (409) 747-3084.

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