Journal
NEUROGASTROENTEROLOGY AND MOTILITY
Volume 24, Issue 5, Pages 479-+Publisher
WILEY
DOI: 10.1111/j.1365-2982.2012.01899.x
Keywords
amygdala; colon; corticotropin releasing factor; irritable bowel syndrome; visceral hypersensitivity; Wistar-Kyoto rat
Funding
- Department of Veterans Affairs, USA
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Background Stress worsens abdominal pain experienced by patients with irritable bowel syndrome (IBS), a chronic disorder of unknown origin with comorbid anxiety. Previously, we have demonstrated colonic hypersensitivity in WistarKyoto rats (WKYs), a high-anxiety strain, which models abdominal pain in IBS. In low-anxiety rats, we have demonstrated that the central nucleus of the amygdala (CeA) regulates colonic hypersensitivity and anxiety induced by selective activation of either glucocorticoid receptors (GR) or mineralocorticoid receptors (MR), which is also mediated by the corticotropin releasing factor (CRF) Type-1 receptor. The goal of the present study was to test the hypothesis that the CeA through GR, MR, and/or CRF-1R regulates colonic hypersensitivity in WKYs. Methods One series of WKYs had micropellets of a GR antagonist, an MR antagonist or cholesterol (control) stereotaxically implanted onto the CeA. Another series were infused in the CeA with CRF-1R antagonist, or vehicle. Colonic sensitivity was measured as a visceromotor response (VMR) to graded colorectal distension (CRD). Key Results The exaggerated VMR to graded CRD in WKYs was unaffected by GR or MR antagonism in the CeA. In contrast, direct CeA infusion of CRF-1R antagonist significantly inhibited the VMR to CRD at noxious distension pressures. Conclusions & Inferences Stress hormones in the CeA regulate colonic hypersensitivity in the rat through strain-dependent parallel pathways. The colonic hypersensitivity in WKYs is mediated by a CRF-1R mechanism in the CeA, independent of GR and MR. These complementary pathways suggest multiple etiologies whereby stress hormones in the CeA may regulate abdominal pain in IBS patients.
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