Clermont Université, Université d'Auvergne, NEURO-DOL, BP 10448, F-63000, CLERMONT-FERRAND Inserm, U1107, F-63001 Clermont-Ferrand, France.
Pain. 2012 Aug;153(8):1657-1663. doi: 10.1016/j.pain.2012.04.023. Epub 2012 Jun 2.
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 (10mg/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.
慢性疼痛是一种多维体验,不仅包括伤害感受的变化,还包括情绪和认知功能的障碍。这些后两个组成部分在临床前研究中通常没有被考虑到。我们在慢性缩窄性坐骨神经损伤(CCI)诱导的大鼠神经病理性疼痛模型中研究了情绪和认知障碍。分析了伤害感受反应、焦虑和抑郁样行为以及认知能力,并研究了口服给予度洛西汀和加巴喷丁的效果。在电子 von Frey 测试中,CCI 大鼠表现出机械性超敏反应,度洛西汀(3-30mg/kg)和加巴喷丁(10-30mg/kg)可影响该反应。在社会而非空间(Y 迷宫)识别记忆测试中发现了认知障碍。度洛西汀和加巴喷丁(3-30mg/kg)剂量依赖性地恢复了社会识别记忆障碍。焦虑样行为仅在开阔场测试中观察到(内区时间减少),而在高架十字迷宫或社交互动测试中未在 CCI 动物中观察到。在该测试中,还观察到运动活动的损害(总穿越次数减少)。度洛西汀和加巴喷丁(10mg/kg)可有效增加内区时间和运动活动。CCI 大鼠和假手术大鼠之间在抑郁样行为(蔗糖偏好测试)方面没有差异。这些数据表明,在神经病理性 CCI 大鼠中似乎存在认知而不是情绪障碍,并且度洛西汀和加巴喷丁可以逆转这些障碍。