含泊洛沙姆、藻酸盐及氯化钙的利多卡因复合制剂对大鼠切口伤模型术后镇痛及伤口愈合的影响
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Effects of a Lidocaine-Loaded Poloxamer/Alginate/CaCl2 Mixture on Postoperative Pain and Adhesion in a Rat Model of Incisional Pain
背景与目的
疼痛和伤口愈合是术后常见难题。利多卡因具有止痛和消炎的作用,而poloxamer/海藻酸/cacl2(PACM)是一种常见润滑剂。因此我们假设,利多卡因作为化学屏障以及PACM作为物理屏障,有利于术后镇痛和伤口愈合。本研究的目的是探讨利多卡因混合制剂对老鼠切口伤的影响。主要结局指标评价von Frey filament纤维在不同浓度的利多卡因混合制剂组、PACM制剂组以及空白对照组中MWT(机械缩足反射阈值)差异。
方 法
使用雄性SD大鼠制作术后疼痛模型,在足底形成切口伤后,根据浓度的不同分为不同浓度的利多卡因混合PACM制剂组(0.5%、1%、2%、4%的利多卡因)、PACM组和空白对照组。通过von Frey filament纤维检测血清水平的肿瘤坏死因子、白细胞介素(IL)-1、IL-6和高灵敏度的c反应蛋白等指标来进行MWT的判定。并通过用显微镜观察术后两周使用复合制剂涂抹的大鼠了炎症和纤维化的变化,最后采用Bonferroni矫正方法对数据进行了统计学分析。
结 果
多因数分析显示,在手术后6到8个小时4% 利多卡因混合制剂与S和C组相比,MWT 显著提高;在手术后4小时,2% 利多卡因混合制剂与S和C组相比显著增加.线性混合效应模型显示,与P组相比MWT(平均值[95%置信区间]的估计差异)在PL2和PL4组中明显增高,(6.58 [2.52-10.63],P = .002; 11.46 [7.40-15.51],P <0.001);显微镜观察显示,与S组相比,PL2组和PL4组的炎症反应和纤维化明显降低,在手术后1,2,48小时和2周后,与S组或P组相比,利多卡因混合制剂组血清水平的肿瘤坏死因子-α,IL-1β,IL-6和高敏C反应蛋白的均分别降低。
结 论
利多卡因复合PACM制剂可以缓解术后疼痛,其中利多卡因增强了PACM的促愈合作用。
原始文献摘要
Choi, Geun Joo; Kang, Hyun; Hong, Min Eui; Effects of a Lidocaine-Loaded Poloxamer/Alginate/CaCl2 Mixture on Postoperative Pain and Adhesion in a Rat Model of Incisional Pain Anesthesia & Analgesia . 125(1):320-327, July 2017.
BACKGROUND:
Pain and adhesion are problematic issues after surgery. Lidocaine has analgesics and anti-inflammatory properties, and poloxamer/alginate/CaCl2 (PACM) is a known antiadhesive agent. We hypothesized that the novel combination of lidocaine as chemical barrier and PACM as physical barrier would be beneficial for both postoperative pain and adhesion. The purpose of this study was to investigate the effects of lidocaine-loaded PACM in a rat model of incisional pain. Primary outcome was to evaluate between-group differences for the mechanical withdrawal threshold (MWT) measured by von Frey filament in various concentrations of lidocaine-loaded PACM applied, PACM applied, and sham-operated groups.
METHODS:
Male Sprague-Dawley rats were used for the postoperative pain model. After plantar incision and adhesion formation, 0.5%, 1%, 2%, and 4% lidocaine-loaded PACM, PACM only, nothing, and 4% lidocaine only were applied at the incision site in groups PL0.5, PL1, PL2, PL4, P, S, and L4, respectively. MWT using a von Frey filament and serum levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and high-sensitivity C-reactive protein were measured. Rats were euthanized 2 weeks after surgery, and inflammation and fibrosis were assessed with microscopy. Data were analyzed using the Kruskal–Wallis test, multivariate analysis of variance, and linear mixed-effect model. To compare MWT at each time point, analysis of variance with Bonferroni correction was used.
RESULTS:
Multivariate analysis of variance showed that 4% lidocaine-loaded PACM significantly raised the MWT up to 6 and 8 hours after surgery compared with lidocaine-unloaded groups S and P, respectively; 2% lidocaine-loaded PACM significantly increased the MWT at 4 hours after surgery compared with groups S and C. Linear mixed-effect model showed that the MWT (estimated difference in means [95% confidence interval]) was significantly increased in groups PL2 and PL4 (6.58 [2.52–10.63], P = .002; 11.46 [7.40–15.51], P < .001, respectively) compared with group P. Inflammation and fibrosis seen on microscopic evaluation were significantly decreased in groups PL2 and PL4 compared with group S. Four percent of lidocaine only showed a significant reduction in inflammation. Serum levels of tumor necrosis factor-α, IL-1β, IL-6, and high-sensitivity C-reactive protein were decreased in lidocaine-loaded groups compared with group S or P at 1, 2, and 48 hours, and 2 weeks after surgery, respectively.
CONCLUSIONS:
Lidocaine-loaded PACM reduced postoperative pain, and lidocaine strengthened the antiadhesive effect of PACM.
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