HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/G1033    most recent 00507.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Larauche, M. Articles by McRoberts, J. A. Search for Related Content PubMed PubMed Citation Articles by Larauche, M. Articles by McRoberts, J. A.

NEUROREGULATION AND MOTILITY

Corticotropin-releasing factor type 1 receptors mediate the visceral hyperalgesia induced by repeated psychological stress in rats

¹Department of Medicine, ²Center for Neurovisceral Sciences and Women's Health, ³Center for Ulcer Research and Education: Digestive Disease Research Center, ⁵Departments of Physiology, Psychiatry, and Behavioral Sciences, and ⁶Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles; ⁴Veterans Affairs, Greater Los Angeles Healthcare System, Los Angeles, California; and ⁷GlaxoSmithKline (Neurology and Gastrointestinal Centre for Excellence for Drug Discovery), Harlow, United Kingdom

Submitted 2 November 2007 ; accepted in final form 25 February 2008

Visceral hypersensitivity has been implicated as an important pathophysiological mechanism in functional gastrointestinal disorders. In this study, we investigated whether the sustained visceral hyperalgesia induced by repeated psychological stress in rats involves the activation of CRF₁ signaling system using two different antagonists. Male Wistar rats were exposed to 10 consecutive days of water avoidance stress (WAS) or sham stress for 1 h/day, and the visceromotor response to phasic colorectal distension (CRD) was assessed before and after the stress period. Animals were injected subcutaneously with the brain penetrant CRF₁ antagonist, CP-154,526, acutely (30 min before the final CRD) or chronically (via osmotic minipump implanted subcutaneously, during stress) or with the peripherally restricted, nonselective CRF₁ and CRF₂ antagonist, astressin, chronically (15 min before each stress session). Repeated WAS induced visceral hypersensitivity to CRD at 40 and 60 mmHg. CP-154,526 injected acutely significantly reduced stress-induced visceral hyperalgesia at 40 mmHg but not at 60 mmHg. Chronic subcutaneous delivery of astressin reduced the stress-induced visceral hyperalgesia to baseline at all distension pressures. Interestingly, chronically administered CP-154,526 eliminated hyperalgesia and produced responses below baseline at 40 mmHg and 60 mmHg, indicating a hypoalgesic effect of the compound. These data support a major role for CRF₁ in both the development and maintenance of visceral hyperalgesia induced by repeated stress and indicate a possible role of peripheral CRF receptors in such mechanisms.

visceral nociception; astressin; CP-154,526; water avoidance

This article has been cited by other articles:

				A. D. Farmer and Q. Aziz Visceral pain hypersensitivity in functional gastrointestinal disorders Br. Med. Bull., September 1, 2009; 91(1): 123 - 136. [Abstract] [Full Text] [PDF]

				M. Larauche, G. Gourcerol, L. Wang, K. Pambukchian, S. Brunnhuber, D. W. Adelson, J. Rivier, M. Million, and Y. Tache Cortagine, a CRF1 agonist, induces stresslike alterations of colonic function and visceral hypersensitivity in rodents primarily through peripheral pathways Am J Physiol Gastrointest Liver Physiol, July 1, 2009; 297(1): G215 - G227. [Abstract] [Full Text] [PDF]

				S. Sweetser, M. Camilleri, S. J. Linker Nord, D. D. Burton, L. Castenada, R. Croop, G. Tong, R. Dockens, and A. R. Zinsmeister Do corticotropin releasing factor-1 receptors influence colonic transit and bowel function in women with irritable bowel syndrome? Am J Physiol Gastrointest Liver Physiol, June 1, 2009; 296(6): G1299 - G1306. [Abstract] [Full Text] [PDF]

				S. Bradesi, V. Martinez, L. Lao, H. Larsson, and E. A. Mayer Involvement of vasopressin 3 receptors in chronic psychological stress-induced visceral hyperalgesia in rats Am J Physiol Gastrointest Liver Physiol, February 1, 2009; 296(2): G302 - G309. [Abstract] [Full Text] [PDF]

				C. Chotiwat and R. B. S. Harris Antagonism of specific corticotropin-releasing factor receptor subtypes selectively modifies weight loss in restrained rats Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2008; 295(6): R1762 - R1773. [Abstract] [Full Text] [PDF]