| 右美托咪定对神经病理性疼痛的作用及其机制 |
| 投稿时间：2018-09-03 修订日期：2018-10-13 点此下载全文 |
| 引用本文：杨颖聪,夏中元,孟庆涛,刘康,赵博.右美托咪定对神经病理性疼痛的作用及其机制[J].医学研究杂志,2018,47(7):78-83 |
| DOI：
10.11969/j.issn.1673-548X.2018.07.019 |
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| 中文摘要:目的 观察右美托咪定对坐骨神经结扎所致神经病理性疼痛的镇痛作用，从离子通道角度探讨其机制。方法 SD大鼠随机分为3组：CCI组、CCI+Dex组及Sham组，每组9只。CCI组和CCI+Dex组通过结扎坐骨神经建立神经病理性疼痛模型，Sham组只暴露坐骨神经不结扎。术后7天，CCI+Dex组腹腔注射右美托咪定40μg/kg，CCI组腹腔注射等量生理盐水，1次/天，连续3天。大鼠术前、CCI术后7天及注药后3天采用Von Frey纤维测定机械性缩足阈值（PWMT），热辐射法测定缩足潜伏期（TWL）。麻醉后处死大鼠，采用酶解法分离大鼠的腰段背根神经节（DRG）细胞，另将HCN1与HCN2质粒转染至HEK293细胞，全细胞膜片钳记录HEK293细胞及大鼠DRG神经元的HCN电流。结果 CCI术后7天，CCI组及CCI+Dex组大鼠PWMT、TWL较术前降低（P<0.05），而Sham组大鼠的PWMT、TWL与术前比较差异无统计学意义（P>0.05）。给药3天后，CCI+Dex组PWMT、TWL较给药前增加（P<0.05）；而CCI组给药前后PWMT和TWL无明显变化。与Sham组比较，CCI组与CCI+Dex组DRG神经元Ih幅度均增加，V1/2值降低（P<0.05）；与CCI组比较，右美托咪定治疗后的大鼠DRG神经元Ih幅度降低，V1/2值增加（P<0.05）。另外右美托咪定（0.1~10μmol/L）抑制HEK 293细胞中的HCN1和HCN2电流，导致最大电流降低，Ih抑制率增加，V1/2向超极化方向改变（P<0.05）。结论 右美托咪定可缓解神经病理性疼痛，这可能与其抑制DRG神经元Ih有关。 |
| 中文关键词:神经病理性疼痛 右美托咪定 背根神经节 超极化激活的环核苷酸门控通道 |
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| Effect and Mechanism of Dexmedetomidine on Neuropathic Pain |
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| Abstract:Objective To examine the effect and mechanism of dexmedetomidine on neuropathic pain. Methods SD rats (n=9 per group) were randomly divided into Group CCI, Group CCI+Dex and Group Sham. The neuropathic pain model was established by performing sciatic nerve ligation in Group CCI and Group CCI+Dex. The sciatic nerve was exposed but not ligated in Group Sham. On day 7 after surgery, Group CCI+Dex rats were intraperitoneally (ip) injected dexmedetomidine(40μg/kg), and Group CCI rats were i.p injected with a similar volume of saline solution. Injections were performed once a day for 3 days. The paw withdrawal threshold to mechanical stimulation (PWMT) and the thermal withdrawal latency (TWL) tests were conducted before operation, on day7 after operation, and after treatment, respectively. After treatment, the L4, L5 DRG neurons of rats were isolated. In addition, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels subtype plasmids were transfected into HEK293 cells. Whole-cell clamp recordings were used to examine the properties of HCN currents(Ih) expressed in HEK293 cells and DRG neurons. Results On day7 after operation, PWMT and TWL of the right hind foot were significantly reduced in Group CCI and Group CCI+Dex(P<0.05) compared with preoperative. No significant differences in PWMT and TWL were observed in Group Sham. After dexmedetomidine administration, PWMT and TWL were significantly increased in rats of group CCI+Dex compared to the values before treatment (P<0.05). After saline treatment, no significant changes were observed in PWMT and TWL in Group CCI. Compared with Group Sham, the Ih amplitude of DRG neurons in Group CCI and Group CCI+Dex was increased, and the V1/2 value was decreased significantly(P<0.05). After treatment with dexmedetomidine, the Ih amplitude in Group CCI+Dex was lower, and the V1/2 value was increased significantly, compared to Group CCI(P<0.05). The slope factors for each group were not significantly different (P>0.05). In addition, dexmedetomidine(0.1-10μmol/L) inhibited HCN1 and HCN2 channel currents in HEK 293 cells; caused a decrease of maximal currents, an increase of inhibition rate of Ih, and a negative shift in V1/2. Conclusion Dexmedetomidine significantly alleviates neuropathic pain. This may be associated with the inhibition of Ih in DRG neurons. |
| keywords:Neuropathic pain Dexmedetomidine Dorsal root ganglion HCN Channel |
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