Increased anxiety-like behaviors in rats experiencing chronic inflammatory pain
Increased anxiety-like behaviors in rats experiencing chronic inflammatory pain
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DOI：
10.1016/j.bbr.2012.01.001
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发表时间：
2012-04-01
影响因子：
2.7
通讯作者：
Gendron, Louis
中科院分区：
文献类型：
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作者：
Parent, Alexandre J.;Beaudet, Nicolas;Gendron, Louis
对于许多患者来说，慢性疼痛通常伴随着焦虑和抑郁等共病，有时会被放大。虽然它代表着重要的挑战，但建立适当的临床前行为模型有助于治疗慢性炎性疼痛和相关精神病理学的药物开发。在这项研究中，我们调查了大鼠是否经历足底注射完全弗氏佐剂（CFA）诱导的持续性炎症疼痛发展焦虑样行为，以及临床使用的镇痛和抗焦虑药物是否能够逆转CFA诱导的焦虑相关表型。这些行为在CFA和盐水处理组中进行了28天的评估，并进行了各种行为测试。CFA诱导的机械性异常性疼痛导致焦虑样行为增加，如以下所证明的：（1）高架十字迷宫（elevated-plus maze）的开放臂中花费的时间百分比和进入次数显著减少，（2）在开放区域（OF）中访问的中心方格的数量减少，以及（3）在社交互动测试（SI）中活跃的社交互动减少。作为运动表现指标的闭合臂中的进入次数和在OF中行进的距离在治疗之间没有差异。我们的结果还表明，在CFA处理的大鼠中，急性给吗啡（3 mg/kg，s.c.）消除触觉异常性疼痛和焦虑样行为，而地西泮（1 mg/kg，s.c.）的急性给药仅逆转焦虑样行为。因此，慢性炎性疼痛诱导的焦虑样行为的药物治疗可以使用多种行为测试进行客观评估。这样的模型可以帮助识别/验证影响疼痛和焦虑认知维度的替代潜在目标。(C)2012爱思唯尔有限公司版权所有。
For many patients, chronic pain is often accompanied, and sometimes amplified, by co-morbidities such as anxiety and depression. Although it represents important challenges, the establishment of appropriate preclinical behavioral models contributes to drug development for treating chronic inflammatory pain and associated psychopathologies. In this study, we investigated whether rats experiencing persistent inflammatory pain induced by intraplantar injection of complete Freund's adjuvant (CFA) developed anxiety-like behaviors, and whether clinically used analgesic and anxiolytic drugs were able to reverse CFA-induced anxiety-related phenotypes. These behaviors were evaluated over 28 days in both CFA- and saline-treated groups with a variety of behavioral tests. CFA-induced mechanical allodynia resulted in increased anxiety-like behaviors as evidenced by: (1) a significant decrease in percentage of time spent and number of entries in open arms of the elevated-plus maze (EPM), (2) a decrease in number of central squares visited in the open field (OF), and (3) a reduction in active social interactions in the social interaction test (SI). The number of entries in closed arms in the EPM and the distance traveled in the OF used as indicators of locomotor performance did not differ between treatments. Our results also reveal that in CFA-treated rats, acute administration of morphine (3 mg/kg, s.c.) abolished tactile allodynia and anxiety-like behaviors, whereas acute administration of diazepam (1 mg/kg, s.c) solely reversed anxiety-like behaviors. Therefore, pharmacological treatment of anxiety-like behaviors induced by chronic inflammatory pain can be objectively evaluated using multiple behavioral tests. Such a model could help identify/validate alternative potential targets that influence pain and cognitive dimensions of anxiety. (C) 2012 Elsevier B.V. All rights reserved.