Gender-related differences in irritable bowel syndrome: Potential mechanisms of sex hormones

Background/AimsEarly adverse life events (EALs) are relevant to irritable bowel syndrome in adulthood. Maternal separation (MS), as one of the EALs, has proved to induce visceral hypersensitivity in adult rats. However, the effect of MS on visceral hypersensitvity from the post-weaning period to adulthood remains unknown. MethodsOne hundred and ten neonatal Sprague-Dawley rats were randomly divided into 2 groups: rats in the MS group were exposed to 3 hours daily MS on postnatal day (PND) 2-14; the normal control (NC) group remained undisturbed. Visceral sensitivity was determined by measuring the visceromotor response to colorectal distention on PND21, 35, and 56. Anxiety-like behaviors were measured by the open field test. ResultsCompared with NC rats, MS rats showed significant visceral hypersensitivity from the post-weaning period to adult. The proportion of visceral hypersensitive rats decreased with age from 87.5% to 70.0% in the female MS group and from 90.0% to 66.7% in the male MS group. The relative VMR ratio of MS and NC on PND21 was higher than PND35 and PND56. MS rats showed decreased ability of movement and exploration to the novel environment in the post-weaning period, obesity in the prepubertal period, and more anxietylike behaviors in adulthood. ConclusionsMS can significantly affect visceral sensitivity and behaviors of rats in different age stages, especially in the post-weaning period. Visceral hypersensitivity of MS rats is more pronounced in the post-weaning period and slightly restored in adults. Thus, visceral hypersensitivity in the post-weaning period might play a more meaningful pathophysiologic role in the formation of adult irritable bowel syndrome.

Section: Discussionsupporting

confidence: 93%

Maternal Separation Induced Visceral Hypersensitivity from Childhood to Adulthood

Zhang

Sun

et al. 2017

“…Many human studies also demonstrated that women are more vulnerable to life stress, anxiety, and present exacerbated IBS symptoms under stress. 20 The reason of the sex-related differences in IBS remains unknown. However, a previous study suggested that the relationship between ovarian and stress hormones may be important in the female predominance of IBS.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, sex-specific differences in stress responses could explain the female predominance of IBS. 20 So far, several studies have focused on sex-specific stress response and visceral hypersensitivity. [21][22][23][24][25][26] To our knowledge, the sex-related differences between all kinds of parameters have not been fully described in a single report.…”

Section: Introductionmentioning

confidence: 99%

Repeated Water Avoidance Stress Alters Mucosal Mast Cell Counts, Interleukin-1β Levels with Sex Differences in the Distal Colon of Wistar Rats

Lee

Kim

et al. 2016

Background/AimsThis study was aimed at evaluating differences in the effects of repeated water avoidance stress (rWAS) on colonic movement, mucosal mast cell counts, cytokine levels, and visceromotor response (VMR) to colorectal distension (CRD) in rats of both sexes. MethodsWistar rats were divided into stress and no-stress groups. Rats in the stress group were exposed to rWAS (1 hr/day) for 10 days. Mucosal mast cells were immunohistochemically stained with anti-mast cell tryptase antibody and counted. The colonic mucosal cytokine levels were measured with enzyme-linked immunosorbent assay. The VMR to CRD (visceral analgesia) was assessed by using a barostat and noninvasive manometry. ResultsThe mean number of fecal pellets in the rWAS group increased significantly as compared with that in the no-stress group in both sexes. After adjustment for body weight, the female rats had a significantly higher pellet output than the male rats. The mucosal mast cell count of the female rWAS group was higher than that of the male rWAS group (13.0 ± 0.9 vs 8.8 ± 0.6; P < 0.001). The colonic mucosal interleukin-1β level was also higher only in the female rats of the rWAS group than in those of the no-stress group. On days 10 and 11, a decrease in VMR to CRD was observed at 40 and 60 mmHg in both sexes of the rWAS group, without a sex-based difference. ConclusionsThe colonic response to stress appeared to be more sensitive in the female rats than in the male rats. However, stress-induced visceral analgesia had no sex-related difference and the underlying mechanism needs to be further evaluated.

“…For example visceral pain disorders such as functional dyspepsia or chronic pelvic pain, somatic pain disorders such as fibromyalgia or migraines, and affective disorders such as chronic fatigue syndrome, anxiety or depression, all have female-predominate sex ratios. 7,78,79 These sex-related differences in symptom expression begin around puberty, with the surge of gonadal hormones, but continues to increase through the mid-forties. 80 Interestingly, the rate of newly diagnosed IBS patients decreases after the age of 50 and the sex ratio for IBS patients is similar in the elderly.…”

Section: Sex Linked Differences In Visceral Sensitivitymentioning

confidence: 99%

Mechanisms of Stress-induced Visceral Pain

Meerveld

Johnson

2018

Evidence suggests that long-term stress facilitates visceral pain through sensitization of pain pathways and promotes chronic visceral pain disorders such as the irritable bowel syndrome (IBS). This review will describe the importance of stress in exacerbating IBS-induced abdominal pain. Additionally, we will briefly review our understanding of the activation of the hypothalamic-pituitary-adrenal axis by both chronic adult stress and following early life stress in the pathogenesis of IBS. The review will focus on the glucocorticoid receptor and corticotropin-releasing hormone-mediated mechanisms in the amygdala involved in stress-induced visceral hypersensitivity. One potential mechanism underlying persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in stress-induced visceral nociception, alterations in DNA methylation and histone acetylation patterns within the brain, have been linked to alterations in nociceptive signaling via increased expression of pro-nociceptive neurotransmitters. This review will discuss the latest studies investigating the long-term effects of stress on visceral sensitivity. Additionally, we will critically review the importance of experimental models of adult stress and early life stress in enhancing our understanding of the basic molecular mechanisms of nociceptive processing. Taken together, the complex clinical phenotype makes recapitulating IBS in rodent models extremely challenging. However, an aim of this review will be to describe how the use of rodent models of adult stress, early life stress (ELS), and a dysregulated HPA axis has improved our understanding of stress in the pathophysiology of IBS. Pathophysiology of Irritable Bowel Syndrome: Activation of the Brain-Gut AxisEvidence from clinical and basic research points to dysregulation of the bidirectional communication between the brain-gut axis in IBS. 21 The brain-gut axis represents a dynamic interplay between central circuits and peripheral mechanisms. The messengers of this complex circuit include neural, endocrine, metabolic, and immune mediators that are activated by central factors such as stress (Fig. 1). Although IBS is not an inflammatory disorder, the immune system plays a role in the pathogenesis of IBS in at least a subset of patients and likely contributes to the etiology of IBS symptoms. 22,23 A subset of IBS patients display a low grade chronic inflammation, and there is also evidence that following an enteric infection and combined with stressful life events, there is an increased risk of developed post-infectious IBS. [24][25][26][27] Clearly, the immune system and inflammatory processes are modulated by the HPA and autonomic nervous systems. In support, IBS patients also show increased number and reactivity of mast cells. 28,29 Data from peripheral blood mononuclear cells, as well as in mucosal biopsies, from IBS patients show that cytokines levels including TNF-α...