Autonomic response to a visceral stressor is dysregulated in irritable bowel syndrome and correlates with duration of disease.

BACKGROUND: Previous studies reported altered autonomic nervous system (ANS) responses in irritable bowel syndrome (IBS) at baseline and to colonic balloon distension. This study examined heart rate variability (HRV) and plasma catecholamines as an index of ANS responsiveness in IBS during flexible sigmoidoscopy (FS) and explored associations of HRV with clinical measures. METHODS: Rome III-positive IBS patients and healthy controls completed questionnaires measuring gastrointestinal and psychological symptoms. Heart rate variability measures were calculated using electrocardiogram (ECG) data at rest and during FS. Plasma catecholamines were measured before and after the FS. Linear mixed effects models were used to compare HRV with IBS status and IBS duration across six time points. Significance was assessed at the 0.05 level. KEY RESULTS: Thirty-six IBS patients (53% F, mean age 37.89) and 31 controls (58% F, mean age 37.26) participated. After adjusting for age, sex, body mass index, and current anxiety symptoms, IBS patients had a non-significant lower cardiovagal tone (P = 0.436) and higher cardiosympathetic balance (P = 0.316) at rest. During FS, controls showed a transient increase in cardiosympathetic balance and decrease in cardiovagal tone. However, IBS patients had significantly less cardiosympathetic and cardiovagal responsiveness both leading up to (P = 0.003, P = 0.005) and following (P = 0.001) this stimulus. Those with longer duration of disease had less cardiosympathetic (P = 0.014) and cardiovagal (P = 0.009) responsiveness than those with shorter duration. No differences in catecholamines between IBS and controls were found. CONCLUSIONS & INFERENCES: Irritable bowel syndrome demonstrated dysregulated ANS responses to a visceral stressor which could be related to disease duration. Therefore, autonomic dysregulation is an objective physiologic correlate of IBS.

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

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.