Stress‐induced visceral hypersensitivity to rectal distension in rats: role of CRF and mast cells

Gué, M.; Rio‐Lacheze, C. Del; Eutamène, Hélène; Théodorou, Vassilia; Fioramonti, Jean; Buéno, Lionel

doi:10.1046/j.1365-2982.1997.d01-63.x

Cited by 261 publications

(214 citation statements)

References 35 publications

(37 reference statements)

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“…Interestingly, nonpeptidic selective CRH-R1 receptor antagonists, such as CP-154,526, CRA-1000, NBI-35 965, NBI-27 914, and antalarmin, injected peripherally, i.c.v., or given orally, blunted the colonic-stimulating effects induced by restraint or social stress, water avoidance or morphine withdrawal (83)(84)(85)(86)(87)(88)(89). These results, combined with in vivo data that confirm that selective non-peptidic CRH-R1 antagonists can inhibit stress or CRH-induced hyperalgesia to colorectal distention (90,91), suggest a therapeutic potential of such compounds in IBS. Given the pro-inflammatory actions mediated by CRH receptors, CRH antagonists could benefit patients with ulcerative colitis, a common disorder characterized by chronic inflammation of the bowel that is related to increased levels of CRH and Ucn 2.…”

Section: Clinical Implications Of Crh-r Antagonistssupporting

confidence: 64%

Corticotropin-releasing hormone receptor antagonists

2006

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Corticotropin-releasing hormone (CRH), CRH-related peptides, and CRH receptors play major roles in coordinating the behavioral, endocrine, autonomic, and immune responses to stress. The wide influence of the CRH system on physiological processes in both brain and periphery implicates the respective peptides in the pathophysiology of numerous disorders characterized by dysregulated stress responses. The potential use of CRH antagonists is presently under intense investigation. Selective antagonists have been used experimentally to elucidate the role of CRH-related peptides in disease processes, such as anxiety and depression, sleep disorders, addictive behavior, inflammatory disorders, acute and chronic neurodegeneration, and preterm labor.European Journal of Endocrinology 155 S85-S91

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Section: Clinical Implications Of Crh-r Antagonistssupporting

confidence: 64%

Corticotropin-releasing hormone receptor antagonists

2006

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“…Physiological responses to WA have been well documented and are accompanied by central CRF release and elevations in plasma ACTH and corticosterone within 30 min (9,45,53). Evidence for acute stressinduced visceral hypersensitivity has been previously demonstrated in normal male Wistar rats following restraint stress (25) and following electrical foot shock (62,64) and in Wistar-Kyoto rats (14). However, in the present study only MS180 animals developed stressinduced visceral hyperalgesia in adult life, consistent with a role for neonatal maternal separation in the manifestation of adult visceral hypersensitivity.…”

Section: Face Validity Of the Modelmentioning

confidence: 94%

“…Although untested in this model, other possibilities underlying the stress-induced visceral hyperalgesia include alterations in dorsal column-mediated pain modulation (2) or sensitization of visceral afferent nerve terminals by autonomically mediated changes in target cells in the colon following acute stress, such as mast cell degranulation (25) or enterochromaffin cell activation (25,26).…”

Section: Construct Validity Of Modelmentioning

confidence: 99%

Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat

Coutinho¹,

Plotsky

Sablad³

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

403

372

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Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat. Am J Physiol Gastrointest Liver Physiol 282: G307-G316, 2002. First published October 3, 2001 10.1152/ajpgi.00240.2001.-This study investigated the combined effect of neonatal maternal separation and acute psychological stress on pain responses in adult rats. Long-Evans dams and their male pups were reared under two conditions: 1) 180 min daily maternal separation (MS180) on postnatal days 2-14 or 2) no handling or separation (NH). At 2 mo of age, visceromotor responses to graded intensities of phasic colorectal distension (10-80 mmHg) at baseline as well as following acute 60 min water avoidance stress (WA) were significantly higher in MS180 rats. Both groups showed similar stress-induced visceral hyperalgesia in the presence of naloxone (20 mg/kg ip). MS180 rats had smaller stress-induced cutaneous analgesia in the tail-flick test compared with NH rats, with a residual naloxone-resistant component. MS180 rats showed an enhanced fecal pellet output following WA or exposure to a novel environment. These data suggest that early life events predispose adult Long-Evans rats to develop visceral hyperalgesia, reduced somatic analgesia, and increased colonic motility in response to an acute psychological stressor, mimicking the cardinal features of irritable bowel syndrome. irritable bowel syndrome; stress; analgesia; naloxone IRRITABLE BOWEL SYNDROME (IBS) is a disorder characterized by chronic abdominal pain and discomfort associated with alterations in bowel habits in the absence of a demonstrable pathology (67). Although IBS is likely a heterogeneous disorder in terms of etiology and pathophysiology, alterations in bowel habits are likely related to alterations in autonomic regulation of the gut, whereas symptoms of abdominal pain and discomfort are thought to involve additional changes in the perception of visceral events, in the form of visceral hyperalgesia or allodynia (46, 48). Additionally, in IBS patients without a concurrent diagnosis of fibromyalgia, visceral hypersensitivity is associated with a normal or diminished somatic pain sensitivity to noxious stimuli (13).Progress in the development of more effective therapies has been hampered due to the lack of animal models that mimic the key features of IBS, in particular the enhanced perception of visceral events. Many investigations have utilized acute inflammatory insults to the gut using agents such as glycerol, mustard oil, acetic acid, or zymosan to produce acute visceral hypersensitivity, thereby mimicking inflammatory bowel disorders. However, IBS is a chronic disorder characterized by the absence of inflammatory changes in the gut mucosa. More recently, several potential IBS models have been reported, all of which mimic certain aspects of the human syndrome (2, 15, 62, 72). They include an early life colon irritation model (2), an adult stress sensitization model (62), and an adult postinfection model in the rat (15) and in the mouse (72). Alt...

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“…In the upper gastrointestinal tract of the rat, intracerebroventricular injection of TRH evokes the same kinds of gastric inflammation and erosions as cold restraint stress. In the large bowel, restraint stress exacerbates nociceptive responses and these effects are associated with increased release of histamine (32). Intracerebroventricular injection of corticotrophin-releasing factor (CRF) mimics the responses to stress.…”

Section: Discussionmentioning

confidence: 99%

Activated Mast Cells Infiltrate in Close Proximity to Enteric Nerves in Diarrhea-predominant Irritable Bowel Syndrome

et al. 2003

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Mast cells (MC) may be one factor influencing the response of visceral afferent nerves to mechanical and chemical stimuli. The aim of this study was to evaluate the degree of infiltration and activity of colonic MC in irritable bowel syndrome (IBS). Biopsy specimens were obtained from the cecum and rectum of 14 diarrhea predominant IBS and 14 normal controls. Electron microscopy was used to determine the number of intact and degranulated colonic MC and to quantify these separately according to the distance between MC and enteric nerves. An increased number of MC in both cecum and rectum in the IBS group in comparison with the control group was demonstrated (p<0.05). Activated MC in close proximity to enteric nerves were significantly increased in both cecum and rectum of the IBS group compared to control group (p<0.005). In addition, activated MC were significantly increased in close proximity to the nerves compared to those in the remote area in both cecum and rectum of the IBS group (p<0.0001). MC were significantly increased and activated in both cecum and rectum of the IBS group compared to controls. MC may play a role in the gut sensory hypersensitivity of IBS.

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Stress‐induced visceral hypersensitivity to rectal distension in rats: role of CRF and mast cells

Abstract: Stress enhances abdominal contractions in response to rectal distension in rats via pathways involving central CRF and intestinal mast cells.

Cited by 261 publications

References 35 publications

Corticotropin-releasing hormone receptor antagonists

Corticotropin-releasing hormone receptor antagonists

Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat

Activated Mast Cells Infiltrate in Close Proximity to Enteric Nerves in Diarrhea-predominant Irritable Bowel Syndrome

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