Amitriptyline reverses hyperalgesia and improves associated mood-like disorders in a model of experimental monoarthritis
Amitriptyline reverses hyperalgesia and improves associated mood-like disorders in a model of experimental monoarthritis
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DOI：
10.1016/j.bbr.2014.02.003
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发表时间：
2014-05-15
影响因子：
2.7
通讯作者：
Pinto-Ribeiro, F.
中科院分区：
文献类型：
--
作者：
Amorim, D.;David-Pereira, A.;Pinto-Ribeiro, F.
情感障碍是慢性炎性疼痛的常见合并症，在初级保健中经常被忽视。由于炎症性疼痛对动物模型中情绪样障碍的影响尚不清楚，我们的目的是评估长期实验性单关节炎（阿尔斯）是否诱导啮齿动物焦虑和抑郁样行为的发展，以及阿米替林（一种常用于治疗慢性疼痛的抗抑郁药）是否可以逆转伤害性和情绪样障碍。通过将高岭土/角叉菜胶注射到右膝关节中诱导实验性阿尔斯，对照（SHAM）动物注射盐水。诱导后4周，阿尔斯动物表现出机械性痛觉过敏和抑郁样表型，因为它们在强迫游泳试验中表现出不动性显著增加和不动性潜伏期减少，但花费的攀爬/游泳时间减少。与对照组相比，阿尔斯动物还显示出蔗糖偏好降低，快感缺乏和焦虑样行为指数，因为探索高架十字迷宫开放臂的时间减少。焦虑样表型也得到了旷场中粪便团数量增加的支持。在阿尔斯动物中，阿米替林给药降低了机械性痛觉过敏，增加了蔗糖偏好和攀爬时间，尽管它对对照动物的表现有有害影响。我们的数据表明，这种阿尔斯模型可以用于慢性疼痛-情绪障碍共病的研究，阿米替林能够部分逆转相关的伤害性和情绪障碍。(c)2014爱思唯尔有限公司版权所有。
Affective disorders are common comorbidities of chronic inflammatory pain that are often overlooked in primary care. As the impact of inflammatory pain upon mood-like disorders in animal models is not well known, our objective was to assess whether prolonged experimental monoarthritis (ARTH) induced the development of anxiety and depressive-like behaviours in rodents and if amitriptyline, an antidepressant commonly used in the treatment of chronic pain, could reverse both nociceptive and mood-like impairments. Experimental ARTH was induced through an injection of kaolin/carrageenan into the right knee joint with control (SHAM) animals injected with saline. Four weeks after induction, ARTH animals displayed mechanical hyperalgesia and a depressive-like phenotype as they showed a significant increase in immobility and a decrease in the latency to immobility in the forced-swimming test at the expense of the time spent climbing/swimming. ARTH animals also displayed a decreased sucrose preference, an index of anhedonia and anxiety-like behaviour as time spent exploring the open arms of the elevated-plus-maze was decreased when compared to controls. The anxiety-like phenotype was also supported by an increase in the number of fecal boli left in the open field. In ARTH animals, the administration of amitriptyline decreased mechanical hyperalgesia and increased sucrose preference and the time spent climbing, although it had a deleterious effect in the performance of control animals. Our data show that this model of ARTH can be useful for the study of chronic pain-mood disorders comorbidities and that amitriptyline is able to partly reverse the associated nociceptive and emotional impairments. (c) 2014 Elsevier B.V. All rights reserved.