Animal models of gastrointestinal and liver diseases. Animal models of visceral pain: pathophysiology, translational relevance, and challenges

Meerveld, Beverley Greenwood‐Van; Prusator, Dawn K.; Johnson, Anthony C.

doi:10.1152/ajpgi.00463.2014

Cited by 72 publications

(71 citation statements)

References 272 publications

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“…We recently reviewed the most relevant rodent models, along with potential mediators of visceral pain and the reader is referred to this review, Greenwood-Van Meerveld et al 109 …”

Section: Models Of Stress-induced Visceral Hypersensitivity In Rodentsmentioning

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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“…We recently reviewed the most relevant rodent models, along with potential mediators of visceral pain and the reader is referred to this review, Greenwood-Van Meerveld et al 109 …”

Section: Models Of Stress-induced Visceral Hypersensitivity In Rodentsmentioning

confidence: 99%

Mechanisms of Stress-induced Visceral Pain

Meerveld

Johnson

2018

J Neurogastroenterol Motil

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“…1 Even though the syndrome is defined by chronically recurring abdominal pain and discomfort associated with altered bowel habits in the absence of organic disease, increased trait anxiety, as well as comorbidity with psychiatric and other chronic pain syndromes are common. 2 Despie an extensive body of reported information about peripheral 3–5 and central 6–9 mechanisms involved in the pathophysiology of IBS symptoms, and the development of animal models with high face and construct validity (that is, the models have many features similar to and is based on a similar pathophysiological concept as the human disease), 10 no comprehensive disease model has emerged that would guide the development of novel and effective therapies. This aspect is surprising in view of the comprehensive data as well as clinical experience demonstrating the strong relationship between psychosocial factors and IBS symptoms, 11 and in view of breakthroughs in the identification of several IBS-related biological abnormalities at several levels: the gut epithelium; 12 immune system; 4,5 neuroendocrine mechanisms; 13 brain structure and function; 7 stress response; 14 affective, 8,15 cognitive 6,16–18 and pain modulation 19,20 abnormalities; gene polymorphisms; 3 and the gut microbiome.…”

Section: Introductionmentioning

confidence: 99%

Towards a systems view of IBS

Mayer

Labus

Tillisch

et al. 2015

Nat Rev Gastroenterol Hepatol

225

220

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Despite an extensive body of reported information about peripheral and central mechanisms involved in the pathophysiology of IBS symptoms, no comprehensive disease model has emerged that would guide the development of novel, effective therapies. In this Review, we will first describe novel insights into some key components of brain–gut interactions, starting with the emerging findings of distinct functional and structural brain signatures of IBS. We will then point out emerging correlations between these brain networks and genomic, gastrointestinal, immune and gut-microbiome-related parameters. We will incorporate this new information, as well as the reported extensive literature on various peripheral mechanisms, into a systems-based disease model of IBS, and discuss the implications of such a model for improved understanding of the disorder, and for the development of more-effective treatment approaches in the future.

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“…This indicates high effect of CCl 4 with olive oil on liver tissue resulting a liver fibrosis. For group 4 (4 weeks daily injection by CCL 4 and olive oil with ratio 1:1, 3 ml/Kg), the level of AST and ALT increases, and the small reduction in AST/ALT ratio indicates the human body starts to regenerate a liver tissue again but it is not enough to recover the liver damage. So, CCl 4 has a high effect on liver tissue function and this produces liver injury with high rate.…”

Section: Journal Of Neurology and Neuroscience Issn 2171-6625mentioning

confidence: 99%

“…The connection between the autonomic nervous system and gastrointestinal (GI) tract and the role of the autonomic nervous in the liver function has been described before [4]. The liver is affected by both the sympathetic and the parasympathetic nerve systems.…”

Section: Introductionmentioning

confidence: 99%

“…The liver is affected by both the sympathetic and the parasympathetic nerve systems. These nerve systems modulate information regarding hepatic osmolality, glucose concentrations, and lipid concentrations from the brain through the afferent neurons, and the liver receives varieties of signals including blood flow, bile secretion, and metabolism through the efferent neurons [4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

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Non-Invasive Method to Diagnose the Liver Fibrosis by Using Electrospinography

Hassan¹,

Omar²,

El-Sayed³

2017

J Neurol Neurosci

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The liver is stimulated by both sympathetic and the parasympathetic nerve systems (Autonomic nervous system ANS). These nerves are consequent from the splanchnic and vagal nerves that surround the portal vein and hepatic artery. The afferent signals which responsible for glucose level, osmolality and lipid level is delivered from portal vein to Central nervous system (CNS). In other hand the efferent signals came from CNS to liver by using sympathetic nerves to control in liver functions. The IP injection of carbon tetrachloride CCl 4 make a hepatotoxicity for liver cell and this variation will be detected by afferent nerves to CNS. This will make CNS sent efferent signal different from the normal one. The efferent signals from the surface of spinal cord were recorded by using Electrospinogram device, which measure the potential difference for a specific segment which specify liver innervation (T7-T12). Then these signals were used to diagnose changes in liver functions which result in diagnosis liver diseases in non-invasive method by using only two electrodes on the skin surface of specific segment on spinal cord.

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Animal models of gastrointestinal and liver diseases. Animal models of visceral pain: pathophysiology, translational relevance, and challenges

Cited by 72 publications

References 272 publications

Mechanisms of Stress-induced Visceral Pain

Mechanisms of Stress-induced Visceral Pain

Towards a systems view of IBS

Non-Invasive Method to Diagnose the Liver Fibrosis by Using Electrospinography

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