Spinal-, brainstem- and cerebrally mediated responses at- and below-level of a spinal cord contusion in rats: Evaluation of pain-like behavior
Spinal-, brainstem- and cerebrally mediated responses at- and below-level of a spinal cord contusion in rats: Evaluation of pain-like behavior
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DOI：
10.1016/j.pain.2010.08.024
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发表时间：
2010-12-01
期刊：
影响因子：
7.4
通讯作者：
Finnerup, Nanna Brix
中科院分区：
文献类型：
--
作者：
Baastrup, Cathrine;Maersk-Moller, Camilla Charlotte;Finnerup, Nanna Brix
疼痛是脊髓损伤（SCI）的常见后果，严重影响患者的生活质量。因此，在寻找更好的治疗方法时，需要有效的实验模型和方法。通常，实验性疼痛分析依赖于刺激诱发的戒断反应；然而，由于过度活跃的反射回路的发展，这种脊髓介导的反射反应在评估低于水平的脊髓损伤疼痛时可能特别成问题。在本研究中，我们应用并比较了脊髓损伤大鼠模型中不同程度神经轴的冷（丙酮）、静态（冯弗雷丝）和动态机械（软刷）超敏反应。我们诱导了实验性脊髓损伤（MASCIS 25mm体重下降），并评估了脊髓反射（退缩）、脊髓-脑干-脊髓反射（舔、保护、挣扎、发声、跳跃和咬）和大脑依赖行为（场所逃避/回避范式（PEAP））的发展。我们证明了脑干反射和大脑介导的对脊髓损伤水平刺激的厌恶反应的增加，表明在水平上诱发疼痛行为的发展。此外，低于水平的刺激增加了先天反射反应，但没有增加脑干反射或PEAP的厌恶行为，提示痉挛综合征的发展而不是疼痛样行为。虽然脊髓反射测量对于研究脊髓反射通路和脊髓的变化是可以接受的，但它们不适合作为伤害性行为测量。测量脑干组织反应消除了与痉挛综合征相关的偏差，但疼痛需要皮层参与。因此，依赖于皮质结构的方法，如PEAP，是中枢性疼痛动物模型的最佳终点。(C) 2010国际疼痛研究协会。Elsevier B.V.版权所有。
Pain is a frequent consequence of spinal cord injury (SCI) which may profoundly impair the patients' quality of life. Valid experimental models and methods are therefore desirable in the search for better treatments. Usually, experimental pain assays depend on stimulus-evoked withdrawal responses; however, this spinal-mediated reflex response may be particularly problematic when evaluating below-level SCI pain due to the development of hyperactive reflex circuitries. In this study, we applied and compared assays measuring cold (acetone), static (von Frey filaments), and dynamic mechanical (soft brush) hypersensitivity at different levels of the neuroaxis at and below the level of injury in a rat model of SCI. We induced an experimental SCI (MASCIS 25 mm weight-drop) and evaluated the development of spinal reflexes (withdrawal), spinal-brainstem-spinal reflexes (licking, guarding, struggling, vocalizing, jumping, and biting) and cerebral-dependent behavior (place escape/avoidance paradigm (PEAP)). We demonstrated increased brainstem reflexes and cerebrally mediated aversive reactions to stimuli applied at the level of SCI, suggesting development of at-level evoked pain behavior. Furthermore, stimulation below-level increased innate reflex responses without increasing brainstem reflexes or aversive behavior in the PEAP, suggesting development of the spasticity syndrome rather than pain-like behavior. While spinal reflex measures are acceptable for studying changes in the spinal reflex pathways and spinal cord, they are not suited as nociceptive behavioral measures. Measuring brainstem organized responses eliminates the bias associated with the spastic syndrome, but pain requires cortical involvement. Methods depending on cortical structures, as the PEAP, are therefore optimal endpoints in animal models of central pain. (C) 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.