芬太尼可诱导大鼠痛觉过敏与背根神经节促炎因子过表达

Fentanyl induced hyperalgesia and upregulation of pro-inflammatory cytokines in dorsal root ganglions in rats

目的：探索大剂量芬太尼诱导的痛觉过敏模型中，大鼠背根神经节促炎因子的表达。方法：64只雄性SD大鼠分为2组（n ＝32），皮下注射芬太尼60μg／kg或生理盐水共4次，每次注射间隔15 min。注射前1 d和注射后1、2、3、4 h及1～7 d对大鼠进行压尾机械伤害阈值（TFT）和足底热伤害潜时（PWL）测试。注射前1 d和注射后4 h及1、3、5、7 d每组选取4只大鼠处死，取腰段背根神经节（DRG），以酶联免疫吸附法测定前列腺素E2、白介素1－β、白介素6和肿瘤坏死因子α的表达。结果：对照组大鼠的行为学及DRG中促炎因子水平在各个时间点无统计学差异。实验组大鼠注射后1～4 h TFT及PWL值升高，1～3 d降低；DRG促炎因子在注射后1、3、5、7 d表达升高。结论：大剂量芬太尼可引起大鼠痛觉过敏及DRG促炎因子升高。促炎因子表达峰值延迟于痛觉过敏的表现，且持续更长时间，和痛觉过敏无直接相关。

Objective To investigate the expression of pro-inflammatory cytokines in lumbar dorsal root ganglions （DRG） of rats model of high-dose fentanyl induced hyperalgesia. Methods 64 male SD rats were divided into 2 groups （n = 32）, fentanyl group and normal saline （NS） group. The rats were injected with fentanyl （60 μg/kg） or NS 4 times in total subcutaneously with a 15-minute interval. Mechanical and thermal nociception were measured via the tail pressure test （tail flick thresholds, TFT） and paw withdrawal test （paw withdrawal latency, PWL） at 1 day before, at 1, 2, 3 and 4 hour and on 1 ~ 7 day after administration. 4 rats were sacrificed and the lumbar DRG were harvested to analyze the expression of PGE2 , IL-1β, IL-6 and TNF-αvia ELISA. Results There were no significant changes of TFT, PWL and the expression of pro-inflammatory cytokines in DRG compared to baseline of rats in NS group. The value of TFT , PWL in fentanyl group were above the baseline at the 1 ~ 4 hour and below the baseline at 1~3 day after fentanyl injections. PGE2 , IL-1β, TNF-α and IL-6 increased on 1,3,5,7 day after fentanyl injections significantly. Conclusions High-dose fentanyl induced significant hyperalgesia and up-regulation of pro-inflammatory cytokines in DRG. The expression pro-inflammatory cytokines peaked later and were more protracted than the change of behavior test and show no direct relationship between the two.