吗啡对卵巢切除术后神经病理性疼痛模型大鼠的镇痛作用

Analgesic effect of morphine on neuropathic pain in ovariectomized rats

目的研究雌激素干预吗啡对神经病理性疼痛的镇痛效应。方法雌性Sprague-Dawley大鼠26只,体重为180～200g,随机分为4组:卵巢切除术+吗啡1μg组(OVX+M组,7只),卵巢切除术+0.9%氯化钠溶液组(OVX+S组,6只),卵巢切除假手术+吗啡1μg组(OVX-sham+M组,7只),卵巢切除假手术+0.9%氯化钠溶液组(OVX-sham+S组,6只)。双侧卵巢切除术或假手术后21d,所有大鼠行左侧坐骨神经分支选择结扎切断术,疼痛模型建立14d后鞘内注射吗啡或0.9%氯化钠溶液,分别于给药前及给药后30、60、90、120、150、180min采用vonFrey纤毛测定大鼠的机械刺激缩足阈值(PWT值),并予比较。结果鞘内注射吗啡或0.9%氧化钠溶液后,各时间点OVX+M组和OVX-sham+M组的PWT值显著高于OVX+S组和OVX-Sham+S组(P值均<0.01);其中给药后120、150及180min,OVX+M组的PWT值显著高于OVX-sham+M组(P值均<0.01)。而各时间点OVX+S组与OVX-sham+S组PWT值的差异则无统计学意义(P值均>0.05)。结论双侧卵巢切除术后神经病理性疼痛模型大鼠对鞘内注射吗啡的镇痛效应敏感性增强,提示雌激素能影响吗啡对慢性病理性疼痛的镇痛作用。

Objective To investigate the modulatory effect of estrogen on the analgesic effect of morphine on neuropathic pain. Methods Twenty-six SD female rats （180-200 g） were randomly assigned to ovariotomy （OVX） ＋ morphine group （n = 7）, OVX ＋ saline group （ n = 6）, OVX-sham ＋ morphine group （n = 7）, and OVX-sham＋ saline group （n=6）. All rats received spared nerve injury （SNI） surgery on left leg three weeks after ovariotomy. Fourteen days after SNI operation 1μg morphine or the vehicle （saline） was administered intrathecally via a PE-10 formerly implanted tube. Hind paw withdrawal threshold （PWT） was determined with von Frey hairs and compared before and 30, 60, 90, 120, 150 and 180 min after drug injection. Results Intrathecal injection of morphine or 0.9% NaCl solution remarkably increased the PWT in both OVX ＋ morphine group and OVX-sham＋ morphine group at all time points when compared with their control groups（ P〈0.01 ）. There were significant differences in the PWT between OVX＋ morphine group and OVX-sham＋ morphine group at 120, 150 and 180 min after morphine injection, as the thresholds of rats at OVX＋ morphine group were larger than those of OVX- sham＋ morphine group （ P〈0.01 ）. There was no statistical difference in the PWTs between OVX＋saline group and OVX-sham＋ saline group at all time points （P〉0.05）. Conclusion Ovariotomy can increase the sensitivity to morphine analgesic effects on the neuropathic pain, which suggests that estrogen can modulate the analgesic effect of morphine on neuropathic pain.