Peripheral corticotropin releasing hormone mediates post-inflammatory visceral hypersensitivity in rats.

AIM To investigate whether peripheral corticotropin releasing hormone (CRH), which is up-regulated in intestinal inflammation, mediates the post-inflammatory visceral hypersensitivity in a rat model of colitis. METHODS We measured mucosal myeloperoxidase (MPO) activity as a marker of inflammation, plasma CRH level, and abdominal withdrawal reflex (AWR) to colorectal distension as a visceral nociceptive response at 2, 7 and 14 d after the induction of colitis with 4% acetic acid. RESULTS Colonic inflammation, quantified by MPO activity, significantly increased on d 2 and subsided thereafter, which indicated a resolution of inflammation within 7 d. On the contrary, plasma CRH level and AWR score were increased on d 2, remained high on d 7, and returned to control level on d 14. Intraperitoneal injection of a CRH antagonist, astressin (30 mug/kg), significantly attenuated the post-inflammatory visceral hypersensitivity on d 7. Furthermore, intraperitoneal administration of CRH (3 and 10 mug/kg) mimicked the post-inflammatory visceral hypersensitivity in naive rats. CONCLUSION These results suggest that increased peripheral CRH mediates the enhanced visceral nociception in rats recovered from experimental colitis.

[1]  B. Greenwood-Van Meerveld,et al.  Corticotropin‐releasing factor receptor 1‐deficient mice show decreased anxiety and colonic sensitivity , 2007, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[2]  M. Hongo,et al.  Effect of alpha‐helical CRH on quantitative electroencephalogram in patients with irritable bowel syndrome , 2007, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[3]  G. Holtmann,et al.  Severity of mucosal inflammation as a predictor for alterations of visceral sensory function in a rat model , 2006, Pain.

[4]  J. Schulkin,et al.  Long-term expression of corticotropin-releasing factor (CRF) in the paraventricular nucleus of the hypothalamus in response to an acute colonic inflammation , 2006, Brain Research.

[5]  Greg D. Gale,et al.  Corticotropin-releasing factor receptor 1 mediates acute and delayed stress-induced visceral hyperalgesia in maternally separated Long-Evans rats. , 2005, American journal of physiology. Gastrointestinal and liver physiology.

[6]  Y. Taché,et al.  Role of corticotropin-releasing factor pathways in stress-related alterations of colonic motor function and viscerosensibility in female rodents. , 2005, Gender medicine.

[7]  S. L. la Fleur,et al.  Role of peripheral corticotropin-releasing factor and urocortin II in intestinal inflammation and motility in terminal ileum. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[8]  A. Weston,et al.  Terminal ileal mucosal mast cells in irritable bowel syndrome , 1993, Digestive Diseases and Sciences.

[9]  M. Hongo,et al.  Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome , 2004, Gut.

[10]  W. Khan,et al.  Visceral hyperalgesia and intestinal dysmotility in a mouse model of postinfective gut dysfunction. , 2004, Gastroenterology.

[11]  C. Pothoulakis,et al.  Corticotropin-releasing hormone (CRH) requirement in Clostridium difficile toxin A-mediated intestinal inflammation. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Jeom-Yong Kim,et al.  Role of mucosal mast cells in visceral hypersensitivity in a rat model of irritable bowel syndrome. , 2004, Journal of veterinary science.

[13]  G. Gerken,et al.  Long-Term Effects of Transient Chemically Induced Colitis on the Visceromotor Response to Mechanical Colorectal Distension , 2002, Digestive Diseases and Sciences.

[14]  J. La,et al.  Visceral hypersensitivity and altered colonic motility after subsidence of inflammation in a rat model of colitis. , 2003, World Journal of Gastroenterology.

[15]  R. Spiller,et al.  Distinctive clinical, psychological, and histological features of postinfective irritable bowel syndrome , 2003, American Journal of Gastroenterology.

[16]  H. Mertz.  Visceral hypersensitivity , 2003, Alimentary pharmacology & therapeutics.

[17]  C. Pothoulakis,et al.  Corticotropin-releasing hormone antagonists possess anti-inflammatory effects in the mouse ileum. , 2002, Gastroenterology.

[18]  G. Barbara,et al.  A role for inflammation in irritable bowel syndrome? , 2002, Gut.

[19]  M. Delvaux.  Role of visceral sensitivity in the pathophysiology of irritable bowel syndrome , 2002, Gut.

[20]  Y. Taché,et al.  Peripheral CRF activates myenteric neurons in the proximal colon through CRF(1) receptor in conscious rats. , 2002, American journal of physiology. Gastrointestinal and liver physiology.

[21]  S. Lightman,et al.  CRH in chronic inflammatory stress , 2001, Peptides.

[22]  Y. Taché,et al.  Peripheral corticotropin-releasing factor and stress-stimulated colonic motor activity involve type 1 receptor in rats. , 2000, Gastroenterology.

[23]  G. Gebhart.  Visceral pain—peripheral sensitisation , 2000, Gut.

[24]  P. Pasricha,et al.  A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development. , 2000, Gastroenterology.

[25]  C. O'Morain,et al.  Increased mast cells in the irritable bowel syndrome , 2000, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[26]  E. Razin,et al.  Mast Cell-Nerve Interactions. , 2000, News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society.

[27]  L. Buéno,et al.  Pathobiology of visceral pain: molecular mechanisms and therapeutic implications. III. Visceral afferent pathways: a source of new therapeutic targets for abdominal pain. , 2000, American journal of physiology. Gastrointestinal and liver physiology.

[28]  Picard,et al.  Role of kinin B1 and B2 receptors and mast cells in post intestinal infection‐induced hypersensitivity to distension , 1998, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[29]  V. Théodorou,et al.  Stress‐induced visceral hypersensitivity to rectal distension in rats: role of CRF and mast cells , 1997, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[30]  M. Yamauchi,et al.  Local production of corticotropin releasing hormone is increased in experimental intestinal inflammation in rats. , 1996, Gut.

[31]  G. Chrousos,et al.  Corticotropin releasing hormone in colonic mucosa in patients with ulcerative colitis. , 1995, Gut.

[32]  C. Wolfe,et al.  Corticotrophin-releasing hormone (CRH)-binding protein interference with CRH antibody binding: implications for direct CRH immunoassay. , 1995, The Journal of endocrinology.

[33]  T. Takao,et al.  Plasma CRH response to water immersion-restraint stress in rats bearing a hypothalamic knife cut. , 1994, Endocrine journal.

[34]  P. Whorwell,et al.  Symptoms of irritable bowel syndrome in ulcerative colitis in remission , 1983, Gut.

[35]  L. Katz,et al.  Mast cells in inflammatory conditions of the gastrointestinal tract. , 1962, The American journal of gastroenterology.