Effect of emodin on neuropathic pain transmission mediated by P2X2/3 receptor of primary sensory neurons
Effect of emodin on neuropathic pain transmission mediated by P2X2/3 receptor of primary sensory neurons
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DOI：
10.1016/j.brainresbull.2011.01.017
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发表时间：
2011-04-05
影响因子：
3.8
通讯作者：
Liang, Shangdong
中科院分区：
文献类型：
--
作者：
Gao, Yun;Liu, Han;Liang, Shangdong
神经性疼痛是最难治愈的疼痛类型。P2 X（2/3）受体在促进神经病理性疼痛状态下的疼痛传递中起关键作用。大黄素是大黄中的一种天然蒽醌类化合物。本研究探讨了大黄素对神经病理性疼痛状态下P2 X（2/3）受体介导的疼痛传递的影响。采用慢性压迫性损伤（CCI）模型作为神经病理性疼痛模型。大黄素溶于0.5%羧甲基纤维素钠（CMC）作为溶媒。雄性SD大鼠随机分为假手术+溶媒组、CCI +大黄素组和CCI +溶媒组。测定机械性缩足阈和热性缩足潜伏期。采用免疫组化、原位杂交和RT-PCR方法检测L4/L5背根节（DRG）P2 X（2/3）的表达。CCI +溶媒组大鼠机械缩足阈和热缩足潜伏期低于假手术+溶媒组和CCI +大黄素组（p < 0.05），而CCI +溶媒组大鼠L4/L5背根节P2 X（2）和P2 X（3）受体表达高于假手术+溶媒组和CCI +大黄素组（p < 0.05）。双标记荧光免疫组化显示CCI组DRG中P2 X（2）和P2 X（3）的共定位染色较其他两组明显增强。结果表明：与CCI +溶媒组相比，大黄素能减轻CCI大鼠的痛敏，并显著降低CCI +大黄素组L4/L5背根节P2 X（2/3）的表达（p < 0.05）。原位杂交和RT-PCR检测P2 X（2）和P2 X（3）mRNA表达的结果提示大黄素的药理作用机制涉及核酸水平。结果表明，大黄素可抑制初级感觉神经元P2 X（2/3）受体介导的神经病理性痛传递，从而减轻慢性神经病理性痛。(C)2011 Elsevier Inc. All rights reserved.
Neuropathic pain is the most difficult type of pain to cure. The P2X(2/3) receptors play a crucial role in facilitating the transmission of pain at neuropathic pain states. Emodin is a natural anthraquinone in rhubarb. The present research investigated the effects of emodin on the pain transmission in neuropathic pain states that was mediated by P2X(2/3) receptor in primary sensory neurons. Chronic constriction injury (CCI) model was used as neuropathic pain model. Emodin was dissolved in 0.5% sodium carboxymethyl cellulose (CMC) as vehicle. Sprague-Dawley male rats had been randomly divided into Sham + vehicle group, CCI + emodin group, and CCI + vehicle group. Mechanical withdrawal threshold and thermal withdrawal latency were measured. P2X(2/3) expression in L4/L5 dorsal root ganglion (DRG) was detected by immunohistochemistry, in situ hybridization (ISH) and RT-PCR. The mechanical withdrawal threshold and thermal withdrawal latency in CCI + vehicle group were lower than those in Sham + vehicle group and CCI + emodin group (p < 0.05), while P2X(2) and P2X(3) receptor expression of L4/L5 DRG in CCI + vehicle group was higher than those in the other two groups (p < 0.05). The co-local staining of P2X(2) and P2X(3) in the DRG of CCI group appeared to be more intense than that in the DRG of the other two groups with double-label fluorescence immunohistochemistry. The results showed that the application of emodin alleviated the hyperalgesia of CCI rats and significantly decreased the P2X(2/3) expression of L4/L5 DRG in CCI + emodin group compared with that in CCI + vehicle group (p < 0.05). The data of ISH and RT-PCR in P2X(2) and P2X(3) mRNA expression suggest that the pharmacologic mechanism of emodin is involved in the nucleic acid level. The results showed that emodin can inhibit the transmission of neuropathic pain mediated by P2X(2/3) receptor of primary sensory neurons to alleviate chronic neuropathic pain. (C) 2011 Elsevier Inc. All rights reserved.