Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 present 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 that corticosteroids may enhance visceral and somatic sensation via divergent processes originating in the amygdala and involving specific steroid receptor mechanisms.
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PMID:Divergent effects of amygdala glucocorticoid and mineralocorticoid receptors in the regulation of visceral and somatic pain. 1987 99

A common characteristic of irritable bowel syndrome (IBS) is that symptoms, including abdominal pain and abnormal bowel habits, are often triggered or exacerbated during periods of stress and anxiety. However, the impact of anxiety and affective disorders on the gastrointestinal (GI) tract is poorly understood and may in part explain the lack of effective therapeutic approaches to treat IBS. The amygdala is an important structure for regulating anxiety with the central nucleus of the amygdala facilitating the activation of the hypothalamic-pituitary-adrenal axis and the autonomic nervous system in response to stress. Moreover, chronic stress enhances function of the amygdala and promotes neural plasticity throughout the amygdaloid complex. This review outlines the latest findings obtained from human studies and animal models related to the role of the emotional brain in the regulation of enteric function, specifically how increasing the gain of the amygdala to induce anxiety-like behavior using corticosterone or chronic stress increases responsiveness to both visceral and somatic stimuli in rodents. A focus of the review is the relative importance of mineralocorticoid receptor and glucocorticoid receptor-mediated mechanisms within the amygdala in the regulation of anxiety and nociceptive behaviors that are characteristic features of IBS. This review also discusses several outstanding questions important for future research on the role of the amygdala in the generation of abnormal GI function that may lead to potential targets for new therapies to treat functional bowel disorders such as IBS.
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PMID:Role of anxiety in the pathophysiology of irritable bowel syndrome: importance of the amygdala. 2058 74

Symptoms of irritable bowel syndrome (IBS) are exacerbated by stress. Previously, we demonstrated that the stress hormone corticosterone applied directly to the amygdala induced visceral hypersensitivity through the actions of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). However, the involvement of amygdaloid GR and MR in the regulation of visceral sensitivity following psychological stress is unknown; therefore, the goal of the present study was to determine the relative importance of amygdaloid GR and MR in the regulation of visceral sensitivity in a rodent model of behavioral stress. Male F-344 rats were stereotaxically implanted with micropellets bilaterally on the dorsal margin of the amygdala containing the GR antagonist mifepristone, the MR antagonist spironolactone, or cholesterol as a control. Animals were then exposed to 1 h of water-avoidance stress (WAS) or sham stress for 1 day (acute) or 7 days (repeated). Visceral sensitivity was assessed either 1 h or 24 h after the final session of WAS and quantified as the number of contractions of the external abdominal oblique, a visceromotor response, in response to colorectal distension at pressures of 0-60 mmHg. Acute stress induced transient visceral hyperalgesia, which was absent 24 h after WAS and independent of GR and MR. Conversely, repeated WAS induced sustained visceral hyperalgesia that was abolished by specifically targeting the amygdala with GR and MR antagonists. These results demonstrate that the amygdala corticosteroid system plays an essential role in mediating the effects of repeated WAS on visceral sensitivity. Furthermore, our findings suggest that amygdaloid GR and MR may be involved in IBS symptomatology.
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PMID:Differential involvement of amygdala corticosteroid receptors in visceral hyperalgesia following acute or repeated stress. 2205 12