Activation of the extracellular signal-regulated kinase in the amygdala modulates pain perception
Activation of the extracellular signal-regulated kinase in the amygdala modulates pain perception
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DOI：
10.1523/jneurosci.3536-06.2007
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发表时间：
2007-02-14
影响因子：
5.3
通讯作者：
Gereau, Robert W.
中科院分区：
文献类型：
--
作者：
Carrasquillo, Yarimar;Gereau, Robert W.
杏仁核被认为是调节痛觉的神经中枢。大量的解剖学和行为学研究表明，杏仁核的外源性操纵（即，损伤、药物输注）调节对急性伤害性刺激的行为反应;然而，关于杏仁核中的内源性分子变化知之甚少，所述内源性分子变化在类似病理性疼痛状况的持续伤害性刺激期间促成伤害性处理的改变。在本研究中，我们证明了杏仁核的内源性分子变化在调节与持续性炎症相关的持久外周超敏反应中起着至关重要的作用，我们进一步确定了细胞外信号调节激酶（ERK）作为这种行为敏化的分子底物。使用福尔马林试验作为持续性炎症性疼痛的小鼠模型，我们表明，激活ERK在杏仁核是必要的，足以诱导持久的外周触觉刺激的超敏反应。因此，杏仁核中炎症诱导的ERK激活的阻断显著降低了与持续性炎症相关的持久外周超敏反应，并且杏仁核中ERK的药理学激活在没有炎症的情况下诱导外周超敏反应。重要的是，在没有炎症的情况下，杏仁核中ERK激活的阻断并不影响对急性伤害性刺激的反应，这表明杏仁核ERK激活对伤害性反应的调节是持续炎症状态所特有的。总之，我们的研究结果证明了炎症诱导的外周超敏反应中杏仁核中ERK信号级联的功能作用。
The amygdala has been proposed to serve as a neural center for the modulation of pain perception. Numerous anatomical and behavioral studies demonstrate that exogenous manipulations of the amygdala (i.e., lesions, drug infusions) modulate behavioral responses to acute noxious stimuli; however, little is known about the endogenous molecular changes in the amygdala that contribute to alterations in nociceptive processing during persistent noxious stimuli that resemble pathological pain conditions. In the present study, we demonstrate that endogenous molecular changes in the amygdala play a crucial role in modulating long-lasting peripheral hypersensitivity associated with persistent inflammation and we further identify the extracellular signal-regulated kinase (ERK) as a molecular substrate underlying this behavioral sensitization. Using the formalin test as a mouse model of persistent inflammatory pain, we show that activation of ERK in the amygdala is both necessary for and sufficient to induce long-lasting peripheral hypersensitivity to tactile stimulation. Thus, blockade of inflammation-induced ERK activation in the amygdala significantly reduced long-lasting peripheral hypersensitivity associated with persistent inflammation, and pharmacological activation of ERK in the amygdala induced peripheral hypersensitivity in the absence of inflammation. Importantly, blockade of ERK activation in the amygdala did not affect responses to acute noxious stimuli in the absence of inflammation, indicating that modulation of nociceptive responses by amygdala ERK activation is specific to the persistent inflammatory state. Altogether, our results demonstrate a functional role of the ERK signaling cascade in the amygdala in inflammation-induced peripheral hypersensitivity.