Corticotropin-releasing factor type 1 receptors mediate the visceral hyperalgesia induced by repeated psychological stress in rats
Corticotropin-releasing factor type 1 receptors mediate the visceral hyperalgesia induced by repeated psychological stress in rats
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DOI：
10.1152/ajpgi.00507.2007
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发表时间：
2008-04-01
影响因子：
4.5
通讯作者：
McRoberts, James A.
中科院分区：
文献类型：
--
作者：
Larauche, Muriel;Bradesi, Sylvie;McRoberts, James A.
促肾上腺皮质激素释放因子1型受体介导重复心理应激诱导的大鼠内脏痛觉过敏。美国胃肠和肝脏生理学杂志294：G1033-G1040，2008年。首次发表于2008年2月28日; doi：10.1152/ajpgi.00507.2007。内脏超敏反应是功能性胃肠疾病的重要病理生理机制。本研究采用两种不同的拮抗剂，探讨重复心理应激诱导的大鼠持续内脏痛觉过敏是否涉及CRF 1信号系统的激活。雄性Wistar大鼠连续10天暴露于避水应激（WAS）或假应激，每天1小时，并在应激期前后评估对阶段性结直肠扩张（CRD）的内脏运动反应。动物皮下注射脑渗透剂CRF 1拮抗剂CP-154，526，急性（最终CRD前30分钟）或慢性（通过皮下植入的渗透性微型泵，在应激期间），或慢性（每次应激前15分钟）注射外周限制性、非选择性CRF 1和CRF 2拮抗剂astressin。在40和60 mmHg下重复WAS诱导对CRD的内脏高敏感性。急性注射CP-154，526在40 mmHg下显著降低应激诱导的内脏痛觉过敏，但在60 mmHg下不显著。在所有扩张压力下，长期皮下注射astressin可将应激诱导的内脏痛觉过敏降低至基线水平。有趣的是，长期施用CP-154，526消除了痛觉过敏，并在40 mmHg和60 mmHg下产生低于基线的反应，表明该化合物的痛觉减退作用。这些数据支持CRF 1在重复应激诱导的内脏痛觉过敏的发展和维持中的重要作用，并表明外周CRF受体在这种机制中可能发挥作用。
Corticotropin-releasing factor type 1 receptors mediate the visceral hyperalgesia induced by repeated psychological stress in rats. Am J Physiol Gastrointest Liver Physiol 294: G1033-G1040, 2008. First published February 28, 2008; doi:10.1152/ajpgi.00507.2007.- 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.