Pregabalin attenuates place escape/avoidance behavior in a rat model of spinal cord injury
Pregabalin attenuates place escape/avoidance behavior in a rat model of spinal cord injury
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DOI：
10.1016/j.brainres.2010.11.008
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发表时间：
2011-01-25
期刊：
影响因子：
2.9
通讯作者：
Finnerup, Nanna Brix
中科院分区：
文献类型：
--
作者：
Baastrup, Cathrine;Jensen, Troels Staehelin;Finnerup, Nanna Brix
人类的脊髓损伤(SCI)疼痛很难治疗，缺乏有效的方法来衡量行为，可以与临床前复杂的人类疼痛经历相媲美，这是找到更好的治疗这类中枢性疼痛的重要障碍。地点逃避/回避范式(PEAP)依赖于动物对黑暗环境的自然偏好或疼痛缓解之间的主动选择，并被建议测量疼痛的情感动机成分。我们将该方法改进为一种在水平中枢神经病理性疼痛的T10脊髓挫伤模型(SCC)。为了证明对逃避/回避行为变化的敏感性，从而证明PEAP方法在预测药物疗效方面的适用性，我们采用随机设计研究了普瑞巴林(30 mg/kg)治疗的效果。SCC动物在损伤后表现出更多的逃避/回避行为，表明在水平上的机械超敏反应。其次，我们发现SCC动物(高架+迷宫)的状态焦虑水平与PEAP行为之间没有相关性，这表明PEAP测量不会因焦虑水平的差异而产生偏差。第三，我们发现使用止痛药普瑞巴林治疗后，逃避/回避行为减少。因此，PEAP可能适用于作为人类疼痛的替代相关性。总之，这项研究的主要发现是对镇痛剂的药理调节引起的逃避/回避行为变化的敏感性，支持将PEAP作为临床前SCI疼痛研究的中心结果指标。(C)2010爱思唯尔B.V.保留所有权利。
Spinal cord injury (SCI) pain in humans is difficult to treat, and the lack of valid methods to measure behavior comparable to the complex human pain experience preclinically represents an important obstacle to finding better treatments for this type of central pain. The place escape/avoidance paradigm (PEAP) relies on the active choice of an animal between its natural preference for a dark environment or pain relief, and it has been suggested to measure the affective-motivational component of pain. We have modified the method to a T10 spinal cord contusion model (SCC) of at-level central neuropathic pain in Sprague-Dawley rats. In order to demonstrate sensitivity to change in escape/avoidance behavior and thus the applicability of the PEAP method to predict drug efficacy, we investigated the effect of pregabalin (30 mg/kg) treatment in a randomized design. SCC animals displayed increased escape/avoidance behavior postinjury, indicating at-level mechanical hypersensitivity. Second, we found no correlation between state anxiety levels in SCC animals (elevated plus maze) and PEAP behavior, suggesting that the PEAP measurement is not biased by differences in anxiety levels. Third, we demonstrated a decrease in escape/avoidance behavior in response to treatment with the analgesic drug pregabalin. Thus, the PEAP may be applicable as a surrogate correlate of human pain. In conclusion, the primary finding in this study was a sensitivity to change in escape/avoidance behavior induced by pharmacological modulation with analgesics, supporting the use of the PEAP as a central outcome measure in preclinical SCI pain research. (C) 2010 Elsevier B.V. All rights reserved.