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Am J Physiol Gastrointest Liver Physiol (October 29, 2009). doi:10.1152/ajpgi.00298.2009
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Research Article

Divergent Effects of Amygdala Glucocorticoid and Mineralocorticoid Receptors in the Regulation of Visceral and Somatic Pain

Brent Myers1 and Beverley Greenwood-Van Meerveld2,*

1VAMC 2Oklahoma University HSC

Submitted 21 July 2009 ; revision received 28 October 2009 ; accepted in final form 28 October 2009

ABSTRACT

Elevated amygdala activity and increased responsiveness of the hypothalamic-pituitary-adrenal axis have been observed in irritable bowel syndrome (IBS) patients. Recently, we demonstrated that corticosterone (CORT) placed on the amygdala induced anxiety-like behavior coupled with decreased thresholds for visceral and somatic pain in rats. Moreover, these studies suggested that the effects of CORT were dependent on both the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR); however, the specific contributions of these receptors to the interaction between corticosteroids and the amygdala are still unclear. In the current study, we sought to define the distinct roles of amygdaloid GR and MR in anxiety-like behavior, visceral sensitivity, and somatic sensitivity through selective pharmacological activation. Male Fischer-344 rats received bilateral implants on the dorsal margin of the central amygdala containing the GR agonist dexamethasone (DEX), the MR agonist aldosterone (ALDO), or cholesterol as a control. Our results showed that GR or MR activation significantly reduced open arm exploration on the elevated plus maze, a measure of anxiety-like behavior. ALDO increased the number of abdominal muscle contractions in response to all levels of colorectal distension (CRD). In contrast, DEX only increased visceral sensitivity at noxious levels of CRD. Furthermore, GR but not MR activation reduced somatic pain thresholds measured by the mechanical force required to elicit hindlimb withdrawal. In summary, GR and MR mediated-mechanisms induce anxiety and visceral hypersensitivity; whereas somatic sensitivity involves only GR suggesting corticosteroids may enhance visceral and somatic sensation via divergent processes originating in the amygdala and involving specific steroid receptor mechanisms.

Irritable Bowel Syndrome; Hypothalamic-Pituitary-Adrenal Axis; Pain Sensitivity; Aldosterone



* Oklahoma University HSC beverlry-greenwood{at}ouhsc.edu







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