Importance of epigenetic mechanisms in visceral pain induced by chronic water avoidance stress

Tran, Lee; Chaloner, Aaron; Sawalha, Amr H.; van-Meerveld, Beverley Greenwood

doi:10.1016/j.psyneuen.2012.09.016

Cited by 112 publications

(144 citation statements)

References 51 publications

(65 reference statements)

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“…58,74,75 We then advanced these observations by demonstrating that the water avoidance stressor increased CRH and decreased GR expression in the CeA closely resembling that seen in rats with CORT micropellets on the CeA. 61 In the water avoidance stress model, we found that CRH knockdown in the CeA inhibits the stress-induced visceral hypersensitivity. 72 …”

Section: Amygdala Facilitation Of the Hypothalamic-pituitary-adrenal mentioning

confidence: 74%

“…We found that central administration of trichostatin A (TSA), a histone deacetylase inhibitor, significantly inhibited visceral hypersensitivity in adult rats exposed to repeated WAS. 61 Ours was the first study to demonstrate that stress-induced visceral hypersensitivity involved a central epigenetic mechanism, providing a rationale for future studies investigating whether IBS-like symptomatology involved additional epigenetic mechanisms. Subsequently, visceral hypersensitivity induced by a repeated stressor or by CORT was shown to modify histone acetylation in the brain and spinal cord, leading to specific changes in pro-and anti-nociceptive gene expression.…”

Section: Epigenetic Mechanisms That Contribute To Irritable Bowel Synmentioning

confidence: 88%

“…Subsequently, visceral hypersensitivity induced by a repeated stressor or by CORT was shown to modify histone acetylation in the brain and spinal cord, leading to specific changes in pro-and anti-nociceptive gene expression. 61,62,126 DNA methylation patterns within the brain and an increase in the expression of pronociceptive neurotransmitters have also been seen in a model of stress-induced visceral pain. 61 Through the use of currently available histone deacetylase inhibitors such as TSA and suberoylanilide hydroxamic acid (SAHA), in our laboratory, we showed that subjecting male rats to water avoidance stressinduced visceral hypersensitivity could be inhibited by intracerebroventricular infusions of TSA preceding the stress exposure.…”

Section: Epigenetic Mechanisms That Contribute To Irritable Bowel Synmentioning

confidence: 94%

“…61,62,126 DNA methylation patterns within the brain and an increase in the expression of pronociceptive neurotransmitters have also been seen in a model of stress-induced visceral pain. 61 Through the use of currently available histone deacetylase inhibitors such as TSA and suberoylanilide hydroxamic acid (SAHA), in our laboratory, we showed that subjecting male rats to water avoidance stressinduced visceral hypersensitivity could be inhibited by intracerebroventricular infusions of TSA preceding the stress exposure. 61 In a second study, we examined histone deacetylation in the brain using another model of visceral hypersensitivity induced by stereotaxic application of CORT to the CeA.…”

Section: Epigenetic Mechanisms That Contribute To Irritable Bowel Synmentioning

confidence: 94%

“…[56][57][58][59][60] Our findings have also revealed that a decrease in GR expression could be due to increased methylation (Me) of the GR promoter along with decreased acetylation (Ac) of histone 3 (H3) at the GR promoter. 61,62 The persistent decrease in GR expression decreases the binding of GR to a negative GR response (nGRE) element in the CRH promoter, thus removing GR-induced repression of CRH expression. The loss of the repression of the CRH promoter induced a persistent increase in CRH expression, and inhibiting the increase in CRH expression reversed the stress-induced colonic hypersensitivity.…”

Section: Amygdala Facilitation Of the Hypothalamic-pituitary-adrenal mentioning

confidence: 99%

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Mechanisms of Stress-induced Visceral Pain

Meerveld

Johnson

2018

J Neurogastroenterol Motil

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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...

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Section: Amygdala Facilitation Of the Hypothalamic-pituitary-adrenal mentioning

confidence: 74%

Section: Epigenetic Mechanisms That Contribute To Irritable Bowel Synmentioning

confidence: 88%

Section: Epigenetic Mechanisms That Contribute To Irritable Bowel Synmentioning

confidence: 94%

Section: Epigenetic Mechanisms That Contribute To Irritable Bowel Synmentioning

confidence: 94%

Section: Amygdala Facilitation Of the Hypothalamic-pituitary-adrenal mentioning

confidence: 99%

See 3 more Smart Citations

Mechanisms of Stress-induced Visceral Pain

Meerveld

Johnson

2018

J Neurogastroenterol Motil

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Possible implications of animal models for the assessment of visceral pain

Regmi

Shah

2020

Anim Models and Exp Med

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Visceral pain is the most common but challenging problem seen in clinical patients. Approximately a quarter to a half of the world population experience visceral pain at least once during their life span, which leads to substantial health care costs. 1 Inflammation, ischemia, or mesenteric stretching or distention of the hollow organs of the thoracic, pelvic, or abdominal cavities stimulate the afferent nociceptors to activate the pain pathways. 2 The activated fibers transmit the nociceptive signals to the spinal dorsal horn (SDH) and then to the central nervous system (CNS), resulting in visceral pain. 3 Visceral pain is diffuse in nature and is thereby very difficult to localize. 4,5

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Gastrointestinal Physiology and Function

Meerveld

Johnson

Grundy

2017

Handbook of Experimental Pharmacology

145

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The gastrointestinal (GI) system is responsible for the digestion and absorption of ingested food and liquids. Due to the complexity of the GI tract and the substantial volume of material that could be covered under the scope of GI physiology, this chapter briefly reviews the overall function of the GI tract, and discusses the major factors affecting GI physiology and function, including the intestinal microbiota, chronic stress, inflammation, and aging with a focus on the neural regulation of the GI tract and an emphasis on basic brain-gut interactions that serve to modulate the GI tract. GI diseases refer to diseases of the esophagus, stomach, small intestine, colon, and rectum. The major symptoms of common GI disorders include recurrent abdominal pain and bloating, heartburn, indigestion/dyspepsia, nausea and vomiting, diarrhea, and constipation. GI disorders rank among the most prevalent disorders, with the most common including esophageal and swallowing disorders, gastric and peptic ulcer disease, gastroparesis or delayed gastric emptying, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD). Many GI disorders are difficult to diagnose and their symptoms are not effectively managed. Thus, basic research is required to drive the development of novel therapeutics which are urgently needed. One approach is to enhance our understanding of gut physiology and pathophysiology especially as it relates to gut-brain communications since they have clinical relevance to a number of GI complaints and represent a therapeutic target for the treatment of conditions including inflammatory diseases of the GI tract such as IBD and functional gut disorders such as IBS.

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Importance of epigenetic mechanisms in visceral pain induced by chronic water avoidance stress

Cited by 112 publications

References 51 publications

Mechanisms of Stress-induced Visceral Pain

Mechanisms of Stress-induced Visceral Pain

Possible implications of animal models for the assessment of visceral pain

Gastrointestinal Physiology and Function

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