Tramadol reduces anxiety-related and depression-associated behaviors presumably induced by pain in the chronic constriction injury model of neuropathic pain in rats
Tramadol reduces anxiety-related and depression-associated behaviors presumably induced by pain in the chronic constriction injury model of neuropathic pain in rats
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DOI：
10.1016/j.pbb.2014.06.018
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发表时间：
2014-09-01
影响因子：
3.6
通讯作者：
Treede, Rolf-Detlef
中科院分区：
文献类型：
--
作者：
Caspani, Ombretta;Reitz, Marie-Celine;Treede, Rolf-Detlef
抑郁和焦虑是神经性疼痛（NP）的常见合并症。NP的临床前药理研究为药物对刺激诱发疼痛反射测量的影响提供了丰富的信息。然而，很少有临床前研究关注NP引起的合并症的缓解。在本研究中，我们研究了曲马多对NP模型大鼠伤害反射、抑郁相关和焦虑相关行为的影响。我们用坐骨神经慢性收缩损伤作为神经性疼痛的动物模型。我们采用电子von Frey测试（evF）来测量机械敏感性，升高迷宫测试（EPM）来记录焦虑相关行为，强迫游泳测试（FST）来评估抑郁相关行为。在evF中，CCI大鼠的爪脱阈值（PWT）比假手术大鼠降低82% （P < 0.001）。曲马多使CCI大鼠PWT升高336% (P < 0.001)，使假手术大鼠PWT升高16% （P < 0.05）。在EPM上，CCI大鼠在迷宫张开臂上的时间比假手术大鼠少45% （P < 0.05）。曲马多使CCI大鼠张开双臂时间延长67% (P < 0.05)，对假手术无显著影响。在FST期间，CCI大鼠的静止时间比假手术大鼠长28% （P < 0.01）。曲马多使CCI大鼠的静止时间缩短22% (P < 0.001)，而对假手术无影响。曲马多逆转了由坐骨神经损伤引起的机械敏感性以及焦虑相关和抑郁相关行为的变化，在没有损伤的情况下只有轻微的影响。这些数据表明曲马多可以缓解慢性疼痛及其间接后果和合并症，本研究也为寻求药物对NP主要致残症状影响的药理学研究提供了一个模型。(C) 2014 Elsevier Inc .版权所有
Depression and anxiety are common comorbidities of neuropathic pain (NP). Pharmacological preclinical studies on NP have given abundant information on the effects of drugs on reflex measures of stimulus-evoked pain. However, few preclinical studies focus on relief of comorbidities evoked by NP. In this study, we investigated the effects of tramadol on nociceptive reflex, depression-associated and anxiety-related behaviors in a NP model in rats.We used chronic constriction injury (CCI) of the sciatic nerve as an animal model of neuropathic pain. We performed electronic von Frey tests (evF) to measure mechanical sensitivity, elevated plus maze tests (EPM) to record anxiety-related behaviors and forced swimming tests (FST) to evaluate depression-associated behaviors.In the evF, CCI rats showed a decrease of 82% of the paw withdrawal threshold (PWT) compared to sham (P < 0.001). Tramadol increased the PWT by 336% in CCI rats (P < 0.001) and by 16% in sham (P < 0.05). On the EPM, CCI rats spent 45% less time than sham on the open arms of the maze (P < 0.05). Tramadol increased the time spent on the open arms of CCI rats by 67% (P < 0.05) and had no significant effect on sham. During the FST, CCI rats showed 28% longer immobility than sham (P < 0.01). Tramadol reduced the immobility time in CCI rats by 22% (P < 0.001), while having no effect on sham.Tramadol reversed the changes in mechanical sensitivity as well as anxiety-related and depression-associated behaviors that are caused by injury of the sciatic nerve with only minor effects in the absence of injury. These data suggest that tramadol relieves chronic pain and its indirect consequences and comorbidities, and that this study also is a model for pharmacological studies seeking to investigate the effect of drugs on the major disabling symptoms of NP. (C) 2014 Elsevier Inc All rights reserved.