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急性和反复水回避应激诱导的大鼠内脏镇痛:阿片类物质参与的性别差异。

Visceral analgesia induced by acute and repeated water avoidance stress in rats: sex difference in opioid involvement.

机构信息

Department of Medicine, CURE: Digestive Diseases Research Center and Oppenheimer Family Center for Neurobiology of Stress, Digestive Diseases Division at the University of California Los Angeles, CA 90073, USA.

出版信息

Neurogastroenterol Motil. 2012 Nov;24(11):1031-e547. doi: 10.1111/j.1365-2982.2012.01980.x. Epub 2012 Jul 9.

DOI:10.1111/j.1365-2982.2012.01980.x
PMID:22776034
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3470786/
Abstract

BACKGROUND

Chronic psychological stress-induced alterations in visceral sensitivity have been predominantly assessed in male rodents. We investigated the effect of acute and repeated water avoidance stress (WAS) on the visceromotor response (VMR) to colorectal distension (CRD) and the role of opioids in male and cycling female Wistar rats using a novel non-invasive manometric technique.

METHODS

After a baseline VMR (1st CRD, day 0), rats were exposed to WAS (1 h day(-1) ) either once or for four consecutive days, without injection or with naloxone (1 mg kg(-1) ) or saline injected subcutaneously before each WAS session.

KEY RESULTS

The VMR to CRD recorded on day 1 or 4 immediately after the last WAS was reduced in both females and males. The visceral analgesia was mainly naloxone-dependent in females, but naloxone-independent in males. In non-injected animals, on days 2 and 5, VMR was not significantly different from baseline in males whereas females exhibited a significant VMR increase at 60 mmHg on day 5. Basal CRD and CRD on days 1, 2, and 5 in both sexes without WAS induced similar VMR.

CONCLUSIONS & INFERENCES: When monitored non-invasively, psychological stress induces an immediate poststress visceral analgesia mediated by an opiate signaling system in females while naloxone-independent in males, and hyperalgesia at 24 h after repeated stress only in females. These data highlight the importance of sex-specific interventions to modulate visceral pain response to stress.

摘要

背景

慢性心理应激引起的内脏敏感性改变主要在雄性啮齿动物中进行评估。我们使用一种新的非侵入性测压技术,研究了急性和重复水回避应激(WAS)对雄性和循环雌性 Wistar 大鼠结直肠扩张(CRD)的内脏运动反应(VMR)的影响,以及阿片类物质的作用。

方法

在基线 VMR(第 1 次 CRD,第 0 天)后,大鼠接受单次或连续 4 天 WAS(每天 1 小时),在每次 WAS 前皮下注射纳洛酮(1mg/kg)或生理盐水。

主要结果

在最后一次 WAS 后第 1 天或第 4 天记录的 CRD 对 VMR 在雌性和雄性中均降低。在雌性中,内脏镇痛主要依赖于纳洛酮,但在雄性中则不依赖于纳洛酮。在未注射的动物中,在第 2 天和第 5 天,VMR 与基线相比在雄性中没有显著差异,而雌性在第 5 天 60mmHg 时 VMR 显著增加。在没有 WAS 的情况下,第 1、2 和 5 天的基础 CRD 和 CRD 在两性中均引起相似的 VMR。

结论

当进行非侵入性监测时,心理应激会在雌性中引起应激后立即出现内脏镇痛,这种镇痛是由阿片样物质信号系统介导的,而在雄性中则是非阿片类物质依赖的,并且只有在重复应激后 24 小时才会出现痛觉过敏。这些数据强调了针对特定性别进行干预以调节内脏疼痛对压力的反应的重要性。

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