Effect of tetramethylpyrazine on DRG neuron P2X3 receptor involved in transmitting pain after burn
Effect of tetramethylpyrazine on DRG neuron P2X3 receptor involved in transmitting pain after burn
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DOI：
10.1016/j.burns.2009.04.032
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发表时间：
2010-02-01
期刊：
影响因子：
2.7
通讯作者：
Liang, Shangdong
中科院分区：
文献类型：
--
作者：
Gao, Yun;Xu, Changshui;Liang, Shangdong
烧伤是一种严重的伤害，由此产生的疼痛可能非常严重。阿片类药物是目前治疗烧伤疼痛的主要药物，但阿片类药物存在一定的毒副作用，因此，研究阿片类药物的镇痛机制和镇痛药物的作用机制是目前研究的热点之一。测定大鼠机械缩痛阈值（MWT）和热缩痛潜伏期（TWL），免疫组化检测烧伤皮肤神经末梢P2 X（3）受体的表达。采用全细胞膜片钳技术研究川芎嗪对烧伤大鼠背根神经节（DRG）神经元P2 X受体激动剂激活电流的影响。烧伤后1h，用生理盐水（NS）治疗的Ⅰ、Ⅱ度爪烧伤组MWT和TWL均低于未烧伤对照组，并持续24或96 h，P < 0.01。伤后24 h，TMP治疗组的MWT和TWL较NS治疗组显著升高，与未烧伤对照组相比无显著性差异。与NS治疗组相比，TMP治疗组中的二度爪烧伤的MWT和TWL在48 h时显著增加。72小时后，未发现与未烧伤对照组的值有差异。伤后第3天，NS治疗组大鼠背部Ⅰ度、Ⅱ度烧伤皮肤神经末梢P2 X3受体表达高于其他各组（p < 0.05）。川芎嗪治疗后，治疗组大鼠背部Ⅰ度和Ⅱ度烧伤后神经末梢P2 X（3）受体表达明显减少。NS治疗组背根神经节神经元ATP激活电流（I-ATP）明显高于TMP治疗组和未烧伤对照组（p < 0.05）; TMP治疗组与未烧伤对照组的Ⅱ度背部烧伤之间无显著差异结论：TMP阻断了P2 X（3）受体介导的烧伤痛的伤害性信息传递。(C)2009 Elsevier Ltd和ISBI。All rights reserved.
A burn is a severe injury, and the resulting pain can be very significant. Currently, opioids are the primary method of pain management, but these drugs have side effects; thus, it is of prime focus to research the mechanisms of pain formation and analgesic drugs.Objective: To investigate the effects of tetramethylpyrazine (TMP) on burn pain mediated by the P2X(3) receptor.Methods: First-degree and superficial second-degree burn models were used. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured, and P2X(3) receptor expression on nerve terminals in burn-injured skin were detected by immunohistochemistry. The effects of TMP on the P2X receptor agonist-activated currents in freshly isolated burn-injured rat dorsal root ganglion (DRG) neurons were studied by whole-cell patch-clamp technique.Main Results: One hour following the procedure, MWT and TWL in first and second-degree paw-burns with normal saline (NS) treatment were lower than those in the unburned control group and lasted for 24 or 96 h, respectively (p < 0.01). After 24 h, MWT and TWL in the first-degree paw-burn with TMP treatment were significantly increased as compared with NS treatment; no difference was found when compared to the unburned control group. MWT and TWL in the second-degree paw-burn in the TMP treatment group were significantly increased at 48 h compared to NS treatment. No difference was found with the values for the unburned control group after 72 h. On day 3 after the burn, P2X(3)-receptor expression in the nerve terminal in the burn-injured skin of the first- and second-degree dorsal burns in the NS treatment group was higher than those in other groups (p < 0.05). After treatment with TMP, P2X(3)-receptor expression of the nerve terminal in the first- and second-degree dorsal burns of the TMP treatment group was significantly decreased. ATP-activated currents (I-ATP) on the DRG neurons of the second-degree dorsal burn in the NS treatment group were markedly higher than those in the second-degree dorsal burns in the TMP treatment group and the unburned control group (p < 0.05); there were no significant differences between the second-degree dorsal burn in the TMP treatment group and the unburned control group (P > 0.05).Conclusion: TMP alleviates nociceptive transmission of burn-injury pain mediated by the P2X(3) receptor. (C) 2009 Elsevier Ltd and ISBI. All rights reserved.