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右美托咪定对大鼠内毒素诱导的切口后疼痛加剧的预防作用。

The preventive effects of dexmedetomidine on endotoxin-induced exacerbated post-incisional pain in rats.

作者信息

Yamanaka Daiki, Kawano Takashi, Nishigaki Atsushi, Aoyama Bun, Tateiwa Hiroki, Shigematsu-Locatelli Marie, Locatelli Fabricio M, Yokoyama Masataka

机构信息

Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.

出版信息

J Anesth. 2017 Oct;31(5):664-671. doi: 10.1007/s00540-017-2374-7. Epub 2017 May 24.

Abstract

PURPOSE

Low-grade endotoxin (lipopolysaccharide; LPS) exposure may contribute to the development of exaggerated acute postoperative pain. In the present study, we investigated the possible impact of intraoperative administration of dexmedetomidine (DEX) on LPS-induced postoperative hyperalgesia in a rat incisional pain model.

METHODS

The surgical and sham-surgical animals were randomly divided into saline-treated control, 5.0 mg/kg LPS-treated, 10 µg/kg DEX-treated, and 5.0 mg/kg LPS + 10 µg/kg DEX-treated groups. In the surgical animals, a 1-cm-long plantar incision was made through the skin and fascia under isoflurane anesthesia. The sham-surgical rats were only anesthetized. All treatments were administered by a single intraperitoneal (i.p.) injection 60 min before surgery. Acute postoperative pain was assessed using the Rat Grimace Scale (RGS) one day before surgery (baseline) and at 2 h post incision. In another experiment, the involvement of the α-adrenergic receptor was tested using atipamezole, an α-adrenergic receptor antagonist.

RESULTS

In the sham-surgical animals, the RGS did not increase at 2 h after sham surgery compared with the corresponding baseline values in all groups. In the surgical rats, however, the postoperative RGS value of the LPS group was significantly higher than the control group, indicating LPS-induced postoperative hyperalgesia. Administration of intraoperative DEX could prevent the development of such LPS-induced exacerbated post-incisional pain. In addition, the preventive effects of intraoperative DEX were inhibited by pretreatment with atipamezole.

CONCLUSION

Our findings indicate that intraoperative DEX treatment can prevent LPS-induced exacerbated post-incisional pain via the α-adrenergic receptor signaling pathway.

摘要

目的

低剂量内毒素(脂多糖;LPS)暴露可能导致术后急性疼痛加剧。在本研究中,我们在大鼠切口疼痛模型中研究了术中给予右美托咪定(DEX)对LPS诱导的术后痛觉过敏的可能影响。

方法

将手术组和假手术组动物随机分为生理盐水处理对照组、5.0mg/kg LPS处理组、10μg/kg DEX处理组和5.0mg/kg LPS + 10μg/kg DEX处理组。在手术动物中,在异氟烷麻醉下通过皮肤和筋膜做一个1厘米长的足底切口。假手术大鼠仅接受麻醉。所有处理均在手术前60分钟通过单次腹腔内(i.p.)注射给药。使用大鼠面部表情量表(RGS)在手术前一天(基线)和切口后2小时评估急性术后疼痛。在另一项实验中,使用α-肾上腺素能受体拮抗剂阿替美唑测试α-肾上腺素能受体的参与情况。

结果

在假手术动物中,与所有组的相应基线值相比,假手术后2小时RGS未增加。然而,在手术大鼠中,LPS组的术后RGS值显著高于对照组,表明LPS诱导的术后痛觉过敏。术中给予DEX可预防这种LPS诱导的切口后疼痛加剧。此外,术中DEX的预防作用被阿替美唑预处理所抑制。

结论

我们的研究结果表明,术中DEX治疗可通过α-肾上腺素能受体信号通路预防LPS诱导的切口后疼痛加剧。

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