Carrasquillo Yarimar, Gereau Robert W
Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine, 660 S, Euclid Ave., Campus Box 8054, St, Louis, MO, 63110, USA.
Mol Pain. 2008 Jun 23;4:24. doi: 10.1186/1744-8069-4-24.
The extracellular signal-regulated kinase (ERK) cascade has been shown to be a key modulator of pain processing in the central nucleus of the amygdala (CeA) in mice. ERK is activated in the CeA during persistent inflammatory pain and this activation is both necessary and sufficient to induce peripheral tactile hypersensitivity. Interestingly, biochemical studies show that inflammation-induced ERK activation in the CeA only occurs in the right, but not the left hemisphere. This inflammation-induced ERK activation in the right CeA is independent of the side of peripheral inflammation, suggesting that there is a dominant role of the right hemisphere in the modulation of pain by ERK activation in the CeA. However, the functional significance of this biochemical lateralization has yet to be determined. In the present study, we tested the hypothesis that modulation of pain by ERK signaling in the CeA is functionally lateralized. We acutely blocked ERK activation in the CeA by infusing the MEK inhibitor U0126 into the right or the left hemisphere and then measured the behavioral effects on inflammation-induced mechanical hypersensitivity in mice. Our results show that blockade of ERK activation in the right, but not the left CeA, decreases inflammation-induced peripheral hypersensitivity independent of the side of peripheral injury. These findings demonstrate that modulation of pain by ERK signaling in the CeA is functionally lateralized to the right hemisphere, suggesting a dominant role of the right amygdala in pain processing.
细胞外信号调节激酶（ERK）级联反应已被证明是小鼠杏仁核中央核（CeA）疼痛处理的关键调节因子。在持续性炎性疼痛期间，ERK在CeA中被激活，这种激活对于诱导外周触觉超敏反应既是必要的也是充分的。有趣的是，生化研究表明，炎症诱导的CeA中ERK激活仅发生在右侧半球，而非左侧半球。右侧CeA中这种炎症诱导的ERK激活与外周炎症的部位无关，这表明在通过CeA中ERK激活调节疼痛方面，右侧半球起主要作用。然而，这种生化侧化的功能意义尚未确定。在本研究中，我们测试了CeA中ERK信号传导对疼痛的调节在功能上存在侧化的假设。我们通过将MEK抑制剂U0126注入右侧或左侧半球，急性阻断CeA中的ERK激活，然后测量对小鼠炎症诱导的机械性超敏反应的行为影响。我们的结果表明，阻断右侧而非左侧CeA中的ERK激活，可降低炎症诱导的外周超敏反应，且与外周损伤的部位无关。这些发现表明，CeA中ERK信号传导对疼痛的调节在功能上向右侧半球侧化，提示右侧杏仁核在疼痛处理中起主要作用。
