Selective corticotropin-releasing factor 1 receptor antagonist E2508 reduces restraint stress-induced defecation and visceral pain in rat models

Taguchi, Ryota; Shikata, Kodo; Furuya, Yasubumi; Hirakawa, Tetsuya; Ino, Mitsuhiro; Shin, Kogyoku; Shibata, Hajime

doi:10.1016/j.psyneuen.2016.10.025

Cited by 19 publications

(13 citation statements)

References 42 publications

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“…Further supporting evidence for a role of amygdala CRH in stress-induced visceral sensitivity demonstrated that intra-CeA CRH administration increased colonic sensitivity via CRH 1 receptor activation in stress-naïve male rats (Su et al, 2015 ). Peripheral administration of a CRH 1 antagonists dose-dependently reduced stress-induced colonic sensitivity and decreased stress-induced fecal pellet output (Million et al, 2013 ; Taguchi et al, 2017 ). Similarly, a peripherally restricted CRH 1 agonist induced colonic hypersensitivity in stress-naïve adult male rats while a CRH 2 antagonist was also able to inhibit stress-induced colonic hypersensitivity (Larauche et al, 2009 ; Nozu et al, 2014 ; Mulak et al, 2015 ).…”

Section: Neurotransmitters In Stress Pathways That Modulate Visceral mentioning

confidence: 99%

Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

Meerveld

Johnson

2017

Front. Syst. Neurosci.

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Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS). Early life stress (ELS) is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the 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 visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for stress-induced exacerbation of chronic visceral pain. Additionally, we will review the importance of specific experimental models of adult stress and ELS in enhancing our understanding of the basic molecular mechanisms of pain processing.

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Section: Neurotransmitters In Stress Pathways That Modulate Visceral mentioning

confidence: 99%

Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

Meerveld

Johnson

2017

Front. Syst. Neurosci.

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“…Even though a number of IBS-related factors have been identified in animal and patients studies ( 1 , 12 , 13 , 24 , 25 ), a full landscape of IBS-associated genes at the molecular level is needed to get a comprehensive understanding of IBS pathogenesis. A previous small bowel mucosal gene expression study has reported that both transcriptome expression and immune-related mechanisms are altered in IBS-D patients ( 27 ).…”

Section: Introductionmentioning

confidence: 99%

Transcriptome and methylome profiling in a rat model of irritable bowel syndrome induced by stress

et al. 2018

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Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is associated with psychological stress. However, the full landscape of IBS-related epigenetic factors remains unveiled and needs to be elucidated. The water-avoidance stress (WAS) method was used to induce a rat IBS model. Each rat was monitored, and its defecation and behavior were recorded. Total colon RNA was isolated and subjected to Affymetrix GeneChip analysis. Reduced Representation Bisulfate Sequencing (RRBS) was applied to determine the genome-wide methylation pattern in both IBS and control rats. Rats with IBS egested a significantly increased amount of dry and loose stools compared with the control animals, without significant changes in body weight. Compared with the control group, 309 genes were upregulated and 224 genes were downregulated in the colon of the IBS rats. Notch signaling and focal adhesion were increased in the differentially expressed genes (DEGs). A total of 541 genes had significant lower methylation level and 626 genes had significantly higher methylation level in their promoter regions. Adherens junction and leukocyte transendothelial migration were enriched in the differentially methylated genes (DMGs). Few genes were identified in common in both DEGs and DMGs, suggesting that gene expression was not altered by promoter methylation. Reverse transcription-quantitative polymerase chain reaction validation revealed that the mRNA levels of SSX2IP, PARD3 and VCL were significantly downregulated in the IBS group, in accordance with hypermethylation of their promoters. In summary, the present study used a WAS-induced IBS rat model to provide transcriptome and methylome profiling. Most DEGs were associated with Notch signaling and focal adhesion, and only a few were altered by promoter methylation. The present results demonstrated that psychological stress could influence the integrity of the intestinal mucosa barrier and regulate inflammatory response.

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“…Among the pharmacotherapeutic approaches targeting the mechanisms involved in sensitization are: tricyclic antidepressants (TCAs) such as nortriptyline or amitriptyline, NMDA receptor antagonists, such as ketamine, that target temporal summation and secondary (mechanical) hyperalgesia, and selective balanced serotonin and noradrenaline-reuptake inhibitors (SNRIs), such as duloxetine, which influence descending modulation and potentially opioids, gabapentoids, or calcium channel alpha(2)delta ligands (Nijs et al, 2011;(p.196) Woolf, 2011). Novel pharmacological developments include the potential for CRF modulators in the treatment of prolonged pain syndromes associated with HPA-axis irregularities (Lariviere & Melzack, 2000;Taguchi et al, 2017). Although drugs have shown to have modest beneficial effects in the treatment of chronic pain syndromes, it should be noted that since drugs act centrally, they can also elicit serious side effects.…”

Section: Pharmacotherapeutic Approachesmentioning

confidence: 99%

Stress and Sensitization in Chronic Pain

Veldhuijzen¹,

Middendorp²,

Evers³

et al. 2018

Oxford Scholarship Online

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Stress and sensitization are central concepts in chronic pain. Both can be a consequence and a contributor to the pain experience. This chapter describes the psychobiology of stress and sensitization within a multilevel perspective, indicating the impact of various forms of stress and sensitization on multiple psychoneurobiological processes (i.e., autonomic, endocrine, immune, and central processes) related to chronic pain. As a result of disordered stress regulation, sensitization may occur as a mechanism that explains how acute pain problems can become chronic and how acute pain problems can extend or generalize to other body parts or modalities. The evidence for stress and sensitization as consequences of or as contributors to chronic pain is reviewed, and possible underlying mechanisms are discussed. Next, strategies to reduce stress and sensitization and foster desensitization processes are described. The chapter concludes by introducing a motivational account of chronic pain informed by the stress and sensitization literature.

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Selective corticotropin-releasing factor 1 receptor antagonist E2508 reduces restraint stress-induced defecation and visceral pain in rat models

Cited by 19 publications

References 42 publications

Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

Transcriptome and methylome profiling in a rat model of irritable bowel syndrome induced by stress

Stress and Sensitization in Chronic Pain

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