Study of emotional and cognitive impairments in mononeuropathic rats: Effect of duloxetine and gabapentin
Study of emotional and cognitive impairments in mononeuropathic rats: Effect of duloxetine and gabapentin
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DOI：
10.1016/j.pain.2012.04.023
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发表时间：
2012-08-01
期刊：
影响因子：
7.4
通讯作者：
Ardid, Denis
中科院分区：
文献类型：
--
作者：
Gregoire, Stephanie;Michaud, Vincent;Ardid, Denis
慢性疼痛是一种多维体验，不仅包括伤害性感受的变化，还包括情绪和认知功能的损害。这后两种成分在临床前研究中通常不被考虑。我们研究了一种由坐骨神经慢性压迫损伤(CCI)诱导的神经病理性疼痛模型中的情绪和认知障碍。分析伤害性反应、焦虑和抑郁样行为以及认知能力，并研究口服度洛西汀和加巴喷丁的效果。在电子von Frey试验中，CCI大鼠表现出机械超敏反应，度洛西汀(3~30 mg/kg)和加巴喷丁(10~30 mg/kg)可影响该反应。认知障碍在社会性记忆测试中被发现，但在空间(Y-迷宫)识别记忆测试中没有发现。度洛西汀和加巴喷丁(3-30 mg/kg)剂量依赖性地恢复了小鼠的社会再认记忆损伤。焦虑样行为仅在开场测试(内区停留时间减少)中观察到，但在高架加迷宫或CCI动物的社会互动测试中未观察到。在这项测试中，还观察到运动活动的损害(总穿越次数的减少)。度洛西汀和加巴喷丁(10 mg/kg)均能有效增加小鼠在内区停留的时间和运动能力。假手术组和CCI组大鼠的抑郁样行为(糖精偏好试验)无明显差异。这些数据表明，神经病理性CCI大鼠似乎存在认知障碍，而不是情感障碍，度洛西汀和加巴喷丁可以逆转这一障碍。(C)2012年国际疼痛研究协会。爱思唯尔出版公司版权所有。
Chronic pain is a multidimensional experience that not only includes changes in nociception, but also impairments in emotion and cognitive functions. These last 2 components are not often taken into account in preclinical research. We investigated emotional and cognitive impairments in a model of neuropathic pain in rats induced by chronic constriction injury (CCI) of the sciatic nerve. Nociceptive response, anxiety and depressive-like behaviours as well as cognitive capacities were analysed, and the effect of per os administration of duloxetine and gabapentin was studied. In the electronic von Frey test, CCI rats exhibited mechanical hypersensitivity which can be influenced by duloxetine (3-30 mg/kg) and gabapentin (10-30 mg/kg). Cognitive impairments were found in the social but not in the spatial (Y-maze) recognition memory tests. Duloxetine and gabapentin dose-dependently (3-30 mg/kg) restored social recognition memory impairment. Anxiety-like behaviour was only observed in the open-field test (decrease in the time spent in the inner zone) but not in the elevated plus maze or in the social interactions tests in CCI animals. In this test, impairment in locomotor activity (decrease of the total number of crossing) was also observed. Duloxetine and gabapentin (10 mg/kg) were effective to increase the time spent in the inner zone as well as locomotor activity. No difference was observed in depressive-like behaviour (saccharin preference test) between sham-operated and CCI rats. These data suggest that cognitive rather than emotional impairments seem to be present in neuropathic CCI rats and can be reversed by duloxetine and gabapentin. (C) 2012 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.