Oestrogen increases nociception through ERK activation in the trigeminal ganglion: evidence for a peripheral mechanism of allodynia.
Oestrogen increases nociception through ERK activation in the trigeminal ganglion: evidence for a peripheral mechanism of allodynia.
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DOI：
10.1111/j.1468-2982.2008.01755.x
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发表时间：
2009-05
期刊：
影响因子：
--
通讯作者：
Berman NE
中科院分区：
文献类型：
--
作者：
Liverman CS;Brown JW;Sandhir R;Klein RM;McCarson K;Berman NE
丝裂原活化蛋白激酶，细胞外信号调节激酶（ERK），在慢性疼痛的实验模型中被激活，也被雌激素激活。我们使用了一个已建立的炎症性三叉神经痛模型，将完全弗氏佐剂（CFA）注射到咬肌中，以确定ERK激活是否可能在咀嚼相关的三叉神经痛疾病中发挥作用。我们使用分级单丝测量了咬肌（V3，原发性异常性疼痛）和须垫（V2，继发性异常性疼痛）对刺激的退缩反应。雌激素治疗在炎症的存在下增加了戒断反应的刺激咬肌和胡须垫相比，炎症单独，表明一个附加的影响，炎症和雌激素对原发性和继发性异常性疼痛。我们使用蛋白质印迹和免疫组织化学检测了每个治疗组三叉神经节中ERK的活化。咬肌炎症和雌激素治疗均增加ERK激活，联合治疗具有累加效应。咬肌炎症和雌激素均增加了第1和第2节（V1/2）pERK免疫反应阳性神经元的百分比，与炎症单独治疗相比，联合治疗增加了V1/2的pERK免疫反应。我们立体定向管理ERK拮抗剂U 0126，或无活性的控制U 0124，CFA+E2治疗大鼠的三叉神经节。与U 0124处理的大鼠相比，U 0126降低了对触须垫的机械刺激的戒断反应。由于V3中炎症后V2中的继发性异常性疼痛通过拮抗外周中的ERK活化而减少，因此这些数据表明继发性异常性疼痛的外周组分通过ERK活化介导。
The mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK), is activated in experimental models of chronic pain, and is also activated by oestrogen. We used an established model of inflammatory trigeminal pain, injection of Complete Freund's Adjuvant (CFA) into the masseter muscle, to determine whether ERK activation may play a role in hormone-related trigeminal pain disorders. We measured withdrawal responses to stimulation of the masseter (V3, primary allodynia) and whisker pad (V2, secondary allodynia) using graded monofilaments. Oestrogen treatment in the presence of inflammation increased withdrawal response to stimulation of both masseter and whisker pad compared with inflammation alone, indicating an additive effect of inflammation and oestrogen on both primary and secondary allodynia. We examined ERK activation in trigeminal ganglia from each treatment group using western blot and immunohistochemistry. Both masseter inflammation and oestrogen treatment increased ERK activation, and combined treatment had an additive effect. Both masseter inflammation and oestrogen increased the percentage of pERK immunoreactive neurons in divisions 1 and 2 (V1/2), and combined treatment increased pERK immunoreactivity in V1/2 compared with inflammation alone. We stereotactically administered ERK antagonist U0126, or inactive control U0124, to the trigeminal ganglion of CFA+E2-treated rats. U0126 decreased withdrawal responses to mechanical stimulation of the whisker pad compared with U0124-treated rats. Because the secondary allodynia in V2 after inflammation in V3 was reduced by antagonizing ERK activation in the periphery, these data suggest a peripheral component to secondary allodynia mediated through ERK activation.
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