芬太尼超前镇痛对大鼠背根神经节Nav 1.8表达的影响

INFLUENCE OF FENTANYL INJECTION FOR PREEMPTIVE ANALGESIA ON THE EXPRESSION OF NAV 1.8 IN RAT DORSAL ROOT GANGLIA

目的:不同时间点鞘内注射芬太尼对急性炎性内脏痛大鼠进行超前镇痛,探讨急性炎性内脏痛对Nav 1.8表达的影响及超前镇痛时芬太尼对Nav 1.8的作用。方法:24只雄性(SD)大鼠,用随机数表法随机分为4组(n=6):正常对照组(NS组)、单纯乙酸组(AS组)、芬太尼术前组(FB组)、芬太尼术中组(FL组)。麻醉后L3～4鞘内置管。置管后第3 d,建立急性炎性内脏痛模型。对NS、AS组大鼠鞘内注射0.9%氯化钠注射液25μl,5 min后NS组腹腔内注射0.9%氯化钠注射液10ml/kg,AS组腹腔内注射0.6%乙酸10 ml/kg;FB、FL组腹腔注射0.6%乙酸10 ml/kg,FB组5 min前鞘内注射芬太尼(0.05 mg/ml)25μl,FL组30 min后鞘内注射芬太尼25μl。行为学观察后处死大鼠,取L3～6DRG,测定DRG上Nav 1.8 mRNA及蛋白的表达。结果:(1)行为学结果:与NS组相比,炎性痛各组扭体评分高;AS组扭体评分高于FB组、FL组(P<0.05);FL组高于FB组(P<0.05)。(2)RT-PCR及蛋白印迹结果:与NS组相比,炎性痛各组Nav 1.8 mRNA和蛋白的表达均增加(P<0.05):FB组和FL组增多的程度低于AS组,FL组表达高于FB组(P<0.05)。结论:鞘内注射芬太尼可明显减轻大鼠急性炎性内脏痛,对大鼠DRG上的Nav 1.8产生抑制作用;与急性炎性内脏痛产生后行大鼠鞘内注射芬太尼镇痛相比,鞘内行芬太尼超前镇痛有更好的镇痛效果,且对Nav 1.8的抑制作用更明显。

Objective： To explore the influence of fentanyl injection for preemptive analgesia on the expression of Nay 1.8 in rat dorsal root ganglia （DRG）. Methods： Twenty four male 250-300 g SD rats were randomly divided into 4 groups （n = 6）： normal control group （NS group）, acetic acid group （AS group）, fentanyl before surgery group （FB group） and fentanyl in surgery group （FL group）. After being anaesthetized, the 20 G catheters were introduced intrathecally at the space between L3 and L4, and the model of acute inflammatory visceral pain was established. The rats in NS and AS groups were injected with 0.9% sodium chloride （25 gl） intrathecally, then 5 rain later, the rats in the NS group were injected with 0.9% sodium chloride （10 ml/kg） intraperitoneally, and the rats in the AS group were injected with 0.6% ethanoic acid （10 ml/kg） intraperitoneally. The FB and FL groups were injected with 0.6% ethanoic acid （10 ml/kg） intraperitoneally. The FB group was injected intrathecally with fentanyl （0.05 mg/ml, 25 μl）. 5 min befor ethanoic acid injection. The FL group was injected intrathecally with fentanyl （0.05 mg/ml, 25 μl）. 30min after ethanoic acid injection. The behavior of each group was observed and recorded. After all rats were sacrificed, the rat L3..6 DRG was completely removed for detecting the mRNA and protein expression of Nav 1.8 by RT-PCR and Western blotting test. Results： （1） Ethology： The writhing test scores of AS group, FB group and FL group were higher （P 〈 0.05） compared with NS group. The writhing test scores of FB group and FL group were lower （P 〈 0.05） compared with the AS group The writhing test scores of FL group were higher （P 〈 0.05） than that in FB group. （2） RT-PCR and Western-blot test： The mRNA and protein expression of Nav 1.8 increased in AS group, FB group and FL group （P 〈 0.05） compared with NS group; The level of increase in AS group was higher than that in FB group and FL group. The level of increase in FL group were higher （P 〈 0.05） than that in FB group. Conclusion： Intrathecal fentanyl injection could significantly relieve the acute inflammatory pain in rats. The preemptive analgesic effect of fentanyl was accompanied with an inhibition of the expression of Nav1.8.