Electrophysiological correlates of hyperalgesic priming in vitro and in vivo.
Electrophysiological correlates of hyperalgesic priming in vitro and in vivo.
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DOI：
10.1016/j.pain.2013.07.004
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发表时间：
2013-10
期刊：
影响因子：
7.4
通讯作者：
Levine JD
中科院分区：
文献类型：
--
作者：
Hendrich J;Alvarez P;Joseph EK;Chen X;Bogen O;Levine JD
我们模拟了大鼠从急性疼痛到慢性疼痛的转变。在该模型中（称为痛觉过敏启动），在先前的炎症过程或暴露于炎症介质后形成慢性状态，其中对随后暴露于前列腺素 E2 (PGE2) 的反应的特征是蛋白激酶 Cε 依赖性机械痛觉过敏的显着延长。为了评估启动对伤害感受器功能的影响，我们使用肿瘤坏死因子诱导启动进行了体外膜片钳和体内单纤维电生理学研究。在体外，在从已引发的动物中培养的伤害感受器中观察到的唯一变化是静息膜电位（RMP）的显着超极化； 60 分钟测量的延长致敏作用无法在体外进行测试。然而，与行为发现相辅相成的是，与对照组相比，体内基线机械伤害感受阈值显着升高。将 PGE2 注射到外周感受野 30 分钟后，启动伤害感受器和对照伤害感受器均表现出对机械刺激的增强反应。然而，施用 PGE2 后 60 分钟，引发的伤害感受器对机械刺激的反应进一步增强，但对照伤害感受器则没有。因此，在初级传入伤害感受器水平上，可以证明基线功能的改变和延长的 PGE2 诱导的致敏作用。 Kv7.2 的鞘内反义有助于感觉神经元中的 RMP，可逆地阻止行为和单纤维电生理学实验中启动的表达，表明这些通道与痛觉过敏启动的表达有关。
We have modeled the transition from acute to chronic pain in the rat. In this model (termed hyperalgesic priming) a chronic state develops after a prior inflammatory process or exposure to an inflammatory mediator, in which response to subsequent exposure to prostaglandin E2 (PGE2) is characterized by a protein kinase Cε-dependent marked prolongation of mechanical hyperalgesia. To assess the effect of priming on the function of the nociceptor, we have performed in vitro patch clamp and in vivo single fiber electrophysiology studies using tumor necrosis factor to induce priming. In vitro, the only change observed in nociceptors cultured from primed animals, was a marked hyperpolarization in resting membrane potential (RMP); prolonged sensitization, measured at 60 minutes, could not be tested in vitro. However, complimentary with behavioral findings, in vivo baseline mechanical nociceptive threshold was significantly elevated compared to controls. Thirty minutes after injection of PGE2 into the peripheral receptive field, both primed and control nociceptors showed enhanced response to mechanical stimulation. However, sixty minutes after PGE2 administration the response to mechanical stimulation was further increased in primed but not in control nociceptors. Thus, at the level of the primary afferent nociceptor, it is possible to demonstrate both altered function at baseline and prolonged PGE2-induced sensitization. Intrathecal antisense to Kv7.2, which contributes to RMP in sensory neurons, reversibly prevented the expression of priming in both behavioral and single-fiber electrophysiology experiments, implicating these channels in the expression of hyperalgesic priming.
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DOI：
10.1523/jneurosci.5138-11.2012
发表时间：
2012-02-08
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bogen O;Alessandri-Haber N;Chu C;Gear RW;Levine JD
通讯作者：
Levine JD
体内和男性伤害感受器的体外比较。
影响因子：
4
作者：
Hendrich, Jan;Alvarez, Pedro;Joseph, Elizabeth K.;Ferrari, Luiz F.;Chen, Xiaojie;Levine, Jon D.
通讯作者：
Levine, Jon D.
影响因子：
5
作者：
Blackburn-Munro, G;Jensen, BS
通讯作者：
Jensen, BS
影响因子：
3.4
作者：
Hucho, Tim B.;Dina, Olayinka A.;Levine, Jon D.
通讯作者：
Levine, Jon D.
影响因子：
4.7
作者：
Lang, P. M.;Fleckenstein, J.;Grafe, P.
通讯作者：
Grafe, P.