Pregabalin suppresses nociceptive behavior and central sensitization in a rat trigeminal neuropathic pain model.
Pregabalin suppresses nociceptive behavior and central sensitization in a rat trigeminal neuropathic pain model.
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DOI：
10.1016/j.jpain.2012.11.005
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发表时间：
2013-02
期刊：
影响因子：
4
通讯作者：
Sessle, Barry J.
中科院分区：
文献类型：
--
作者：
Cao, Ye;Wang, Hua;Chiang, Chen-Yu;Dostrovsky, Jonathan O.;Sessle, Barry J.
本研究的目的是确定普瑞巴林是否影响三叉神经病理性疼痛模型中的伤害感受行为和中枢敏化。对成年雄性大鼠进行部分眶下神经横断（p-IONX）或假手术。术前和术后将 von Frey 细丝施加到双侧触须垫上，测试伤害感受退缩阈值。术后第 7 天，在注射普瑞巴林（0.1、1、10、100 mg/kg，腹腔注射）或生理盐水之前和之后 30 分钟、60 分钟、120 分钟、180 分钟和 24 小时进行行为评估。还检查了普瑞巴林或盐水对术后第 7-10 天记录在髓背角的伤害性神经元的机械感受野和反应特性的影响。直到术后第 28 天，在 p-IONX 大鼠中观察到反映双侧机械性异常性疼痛的退缩阈值降低，但在假手术大鼠中则没有。术后第 7 天，普瑞巴林显着且剂量依赖性地逆转 p-IONX 大鼠降低的机械戒断阈值。普瑞巴林还减弱神经元的中枢敏化，这反映在其降低的激活阈值的逆转、对捏/压力的反应增加以及刺激反应功能增强。这项研究首次提供了普瑞巴林减轻三叉神经性疼痛模型特征的机械性异常性疼痛和中枢敏化的文献，并支持其临床用于治疗颅面神经性疼痛。
The aim of this study was to determine whether pregabalin affects nociceptive behavior and central sensitization in a trigeminal neuropathic pain model. A partial infraorbital nerve transection (p-IONX) or sham operation was performed in adult male rats. Nociceptive withdrawal thresholds were tested with von Frey filaments applied to the bilateral vibrissal pads pre-operatively and post-operatively. On post-operative day 7, the behavioral assessment was conducted before and at 30 min, 60 min, 120 min, 180 min, and 24hr after pregabalin (0.1, 1, 10, 100 mg/kg, i.p.) or saline injection. The effects of pregabalin or saline were also examined on the mechanoreceptive field and response properties of nociceptive neurons recorded in the medullary dorsal horn at post-operative day 7–10. Reduced withdrawal thresholds reflecting bilateral mechanical allodynia were observed in p-IONX rats until post-operative day 28, but not in sham-operated rats. At post-operative day 7, pregabalin significantly and dose-dependently reversed the reduced mechanical withdrawal thresholds in p-IONX rats. Pregabalin also attenuated central sensitization of the neurons, as reflected in reversal of their reduced activation threshold, increased responses to pinch/pressure, and enhanced stimulus-response function. This study provides the first documentation that pregabalin attenuates the mechanical allodynia and central sensitization that characterize this trigeminal neuropathic pain model, and supports its clinical use for treating craniofacial neuropathic pain.
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