Neurobiology of early life stress and visceral pain: translational relevance from animal models to patient care

Prusator, Dawn K.; Andrews, Alison; Meerveld, B. Greenwood-Van

doi:10.1111/nmo.12862

Cited by 22 publications

(9 citation statements)

References 140 publications

(159 reference statements)

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“…[1][2][3][4][5][6] Risk factors for IBS include being female and exposure to chronic stress. [7][8][9][10][11] A common feature of IBS is that for many patients, their symptoms are worsened by stress and overlap with other stress disorders, including anxiety, depression, and post-traumatic stress disorder. [12][13][14][15] In support of IBS being a stress-sensitive disorder, there is experimental evidence showing abnormal hypothalamicpituitary-adrenal (HPA) axis reactivity in IBS patients as shown by a heightened HPA response to a corticotropin-releasing hormone (CRH) challenge, and an overall increase in hourly cortisol secretion in IBS compared to controls.…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

Mechanisms of Stress-induced Visceral Pain

Meerveld

Johnson

2018

J Neurogastroenterol Motil

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“…This limitation of bedding material causes disruptions in normal maternal care similar to those exhibited by dams during the MS protocol, however, the limited nesting model does not require removal of pups from the dam at any time during the experimental paradigm. This advantage also eliminates differences in weaning weights seen in the MS model (328). Another model of ELS utilizes neonatal colonic irritation using colonic infusion of mustard oil or repeated CRD in neonates (329).…”

Section: Early Life Stress Models Of Visceral Painmentioning

confidence: 99%

Abdominal pain models: mechanisms and therapies and experimental models

Lucarini¹,

Mannelli²,

Ghelardini³

2020

Pharm Adv

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Chronic or recurrent abdominal pain is the most prevalent gastrointestinal disorder, affecting 10% of the general population, including children and adolescents. It is a common feature of both intestinal functional disorders, like irritable bowel syndrome (IBS), and inflammatory bowel diseases (IBDs). These two conditions often overlap from the clinical point of view since a large subset of IBD patients experience persistent abdominal pain even after reaching remission from the intestinal inflammation, developing a condition called IBS-like. Visceral pain management is a major clinical problem in these patients since the lack of effective and safe drugs. Despite the large number of sufferers, the mechanisms that drive the development and the persistence of chronic abdominal pain remain largely unresolved and this presents a major barrier to progress in the development of new therapies. Chronic abdominal pain often displays a complex nature with mixed nociceptive, inflammatory, emotional and neuropathic components. This is mainly attributable to the intricated regulation of visceral sensitivity which involves many actors in the gut as well as in the peripheral and central nervous systems. In this text we describe the neuroanatomical bases of visceral pain signalling, the pathophysiological mechanisms involved in pain persistence and how current treatments work, including an overview of potential new targets. In the context of drug discovery, the potential advantages and disadvantages of different preclinical models of visceral pain were also discussed.

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“…The link for stress-induced abdominal pain in IBS is not well understood. Some evidence suggests that adverse events at different stages throughout life, and especially early life, sensitize the stress response system leading to peripheral sensitization and abnormal CNS pain processing 40 . Several imaging studies have shown altered activation patterns in brain regions involved in nociception with effects on the ACC, posterior cingulate, prefrontal cortex, insula, thalamus, and somatosensory cortex in patients with IBS in response to rectal distension 41 .…”

Section: Stress and The Gut-brain Axis: Implications In Visceral Painmentioning

confidence: 99%

Recent advances in the pathophysiology of visceral pain in irritable bowel syndrome

Valdez-Moráles¹,

Barrios-García²,

Barajas-Espinosa³

et al. 2019

NGL

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Irritable bowel syndrome (IBS) is the most frequent functional bowel disorder seen by gastroenterologists in their daily practice, accounting for more than 30% of outpatient's visits. Recurrent abdominal pain in the absence of obvious physiological abnormalities is one of the principal symptoms of the IBS and can result in emotional distress and physical disability impacting the quality of life of the patient. This pain can be difficult to treat effectively, as the underlying etiology is not well understood. This review focuses on recent advances in the pathophysiology of visceral pain in IBS and describes the main molecular mechanism of visceral hypersensitivity.

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Neurobiology of early life stress and visceral pain: translational relevance from animal models to patient care

Cited by 22 publications

References 140 publications

Mechanisms of Stress-induced Visceral Pain

Mechanisms of Stress-induced Visceral Pain

Abdominal pain models: mechanisms and therapies and experimental models

Recent advances in the pathophysiology of visceral pain in irritable bowel syndrome

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