Xiong Wei, Wu Rao-Ping, Tan Meng-Xia, Tong Zhou-Jie, He Ling-Kun, Guan Shu, Liu Li-Juan, Yin Can-Can, Shen Yu-Lin, Ge Hui-Xiang, Gao Yun
Affiliated Stomatological Hospital of Nanchang University Nanchang, Jiangxi, P. R. China.
Jiangxi Provincial Key Laboratory of Oral Biomedicine Nanchang, Jiangxi, P. R. China.
Int J Clin Exp Pathol. 2017 Nov 1;10(11):11317-11325. eCollection 2017.
Trigeminal neuralgia (TN) is one of the most intense forms of facial pain. It has been reported that the P2X receptor plays a crucial role in facilitating pain transmission, and the calcitonin-gene-related peptide (CGRP) from trigeminal ganglia (TGs) might perform differing function in nociceptive afferent input transmission. The present study investigated whether emodin can affect TN pain transmission by suppressing the expression of P2X receptors and CGRP in TGs. Chronic constriction injury of the infraorbital branch of the trigeminal nerve (CCI-ION) was used as TN model. The TN rats were randomly divided into the following 4 groups: (1) a sham group (Sham), (2) a sham rats treated with emodin group (TN + E), (3) a TN rats treated with 0.5% sodium carboxymethyl cellulose (CMC) as vehicle group (TN) and (4) a TN rats treated with emodin group (TN + E). The mechanical hyperalgesia threshold of TN rats was tested by Electric Von Frey filaments. The change of the expression of P2X receptors and CGRP in rat's TG was detected with RT-PCR, immunohistochemical staining, and Western blotting. The phosphorylation of p38 and ERK1/2 pathway of TG was detected by Western blotting. After CCI-ION injury, the threshold of mechanical hyperalgesia for the territory of ligated infraorbital nerve in TN group decreased significantly compared with that in sham group. On day 14 after operation of CCI-ION, there was also an evident increase in the expression of P2X receptors and CGRP in the TG of TN group. However after treatment with emodin, the response of mechanical hyperalgesia of TN rats was clearly increased while the enhanced expression of P2X receptor and CGRP in TN rats was significantly decreased. The phosphorylation of p38 and ERK1/2 in TN group was stronger than that in Sham group. But these phosphorylation changes in the TN rats were much weaker after treatment with emodin. In conclusion, P2X receptor may cooperate with CGRP in the pain transmission of TN, and emodin can inhibit the expression and activation of P2X receptor and CGRP in TG to relieve TN.
三叉神经痛（TN）是最剧烈的面部疼痛形式之一。据报道，P2X受体在促进疼痛传递中起关键作用，三叉神经节（TG）中的降钙素基因相关肽（CGRP）在伤害性传入输入传递中可能发挥不同功能。本研究调查了大黄素是否能通过抑制TG中P2X受体和CGRP的表达来影响TN疼痛传递。采用三叉神经眶下支慢性缩窄损伤（CCI-ION）作为TN模型。TN大鼠随机分为以下4组：（1）假手术组（Sham），（2）大黄素处理的假手术大鼠组（TN + E），（3）用0.5%羧甲基纤维素钠（CMC）作为溶剂处理的TN大鼠组（TN）和（4）大黄素处理的TN大鼠组（TN + E）。用电子von Frey细丝测试TN大鼠的机械性痛觉过敏阈值。用RT-PCR、免疫组织化学染色和蛋白质印迹法检测大鼠TG中P2X受体和CGRP表达的变化。用蛋白质印迹法检测TG的p38和ERK1/2通路的磷酸化。CCI-ION损伤后，TN组结扎眶下神经区域的机械性痛觉过敏阈值与假手术组相比显著降低。CCI-ION手术后第14天，TN组TG中P2X受体和CGRP的表达也明显增加。然而，大黄素处理后，TN大鼠的机械性痛觉过敏反应明显增强，而TN大鼠中P2X受体和CGRP的增强表达明显降低。TN组中p38和ERK1/2的磷酸化比假手术组更强。但大黄素处理后，TN大鼠的这些磷酸化变化明显减弱。总之，P2X受体可能与CGRP在TN的疼痛传递中协同作用，大黄素可抑制TG中P2X受体和CGRP的表达及激活以缓解TN。
