Article

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in irritable bowel syndrome

Center for Neurobiology of Stress, David Geffen School of Medicine, University of California, Los Angeles, CA 90073, USA.
Neurogastroenterology and Motility (Impact Factor: 3.59). 09/2008; 21(2):149-59. DOI: 10.1111/j.1365-2982.2008.01171.x
Source: PubMed

ABSTRACT

Enhanced stress responsiveness has been implicated as a potential mechanism contributing to the pathophysiology of irritable bowel syndrome (IBS), and should be reflected in altered function of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. Both of these systems can modulate mucosal immune function. The aims of this study were: (i) to characterize the basal circadian rhythm of adrenocorticotropin hormone (ACTH) and cortisol in IBS vs healthy controls; (ii) to compare stimulated ACTH, cortisol and noradrenaline responses to a pelvic visceral stressor (sigmoidoscopy) in IBS and controls; and (iii) to correlate neuroendocrine responses with colonic mucosal cytokine expression and symptoms in IBS. Two separate studies were conducted in women. In Study 1, basal cortisol levels were analysed in 41 IBS and 25 controls using 24-h collections of plasma ACTH and cortisol (q10 min sampling). In Study 2, 10 IBS patients with diarrhoea (IBS-D) and 10 controls underwent sigmoidoscopy with measurements of stimulated neuroendocrine responses and cytokine mRNA expression in colonic tissue. Basal ACTH levels were significantly blunted (P < 0.05), while basal and stimulated plasma cortisol levels were higher in patients. Basal cortisol levels prior to an experimental visceral stressor positively correlated with anxiety symptoms (P < 0.004), but not IBS symptoms. Irritable bowel syndrome patients with diarrhoea had significantly decreased mRNA expression of mucosal cytokines [interleukin (IL)-2, IL-6] in the sigmoid colon vs controls (P < 0.05). Although dysregulations in stress-responsive systems such as the HPA axis and mucosal immune function are demonstrated in IBS, they do not appear to have a primary role in modulating IBS severity and abdominal pain.

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Available from: Emeran A Mayer, Mar 11, 2014
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    • "Subsets of these patients report stress-related symptom onset or increased severity, have difficulty coping with stressful situations, and suffer from depression and/or anxiety (Arnold et al., 2006; Larauche et al., 2012; Bullones Rodriguez et al., 2013). The comorbidity between mood disorders and chronic pelvic pain is due, in part, to altered functioning of corticotropin-releasing factor (CRF)-responsive regions of the brain, including the hypothalamic–pituitary– adrenal (HPA) axis, which regulates stress response and influences the perception of pain (Heim et al., 1998; Chang et al., 2009; Mayson and Teichman, 2009). Under stressful conditions, CRF is secreted from the paraventricular nucleus (PVN) of the hypothalamus and induces the systemic release of adrenocorticotropic hormone (ACTH) from the anterior pituitary corticotrophs. "
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    • "mechanical allodynia and thermal hyperalgesia (Zhang et al., 2012), and (b) a mouse model of chronic psychosocial stress along with visceral hiperalgesia (Tramullas et al., 2012). This evidence highlights that changes in both the HPA axis activity and the immune function are involved in chronic stress-induced hyperalgesia (Blackburn- Munro and Blackburn-Munro, 2001; Fries et al., 2005; Chang et al., 2009; Sominsky et al., 2013). Yet, it is not completely clear the way the HPA axis, immune and nociceptive functions are connected as to lead to the development of enduring cutaneous pain after repeated exposure to stress. "
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    • "A relationship between ELA and the development of IBS in adulthood has been described in clinical literature and animal models. Furthermore, both ELA and IBS are characterized by female predominance and dysregulation of the HPA axis (Drossman et al., 1997; Whitehead et al., 2002; Dinan et al., 2006; Tarullo and Gunnar, 2006; Hyman et al., 2008; Chang et al., 2009). Therefore, the mechanisms by which ELA induces visceral hypersensitivity likely involve ovarian hormones and signaling within the HPA axis. "
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    Full-text · Article · Feb 2013 · Frontiers in Neuroscience
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