Sex differences in peripheral mu-opioid receptor mediated analgesia in rat orofacial persistent pain model.

Sex differences in peripheral mu-opioid receptor mediated analgesia in rat orofacial persistent pain model.
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大鼠口面部持续性疼痛模型外周 Mu-阿片受体介导镇痛的性别差异

DOI:
10.1371/journal.pone.0122924
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
He X
He X
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bai X;Zhang X;Li Y;Lu L;Li B;He X

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单侧结扎大鼠咬肌前浅部腱(TASM)可引起持续性异常性疼痛。外周μ阿片受体(莫尔)介导的持续性肌源性疼痛镇痛的性别差异还不清楚。在这项研究中,我们研究了(1)局部应用莫尔激动剂是否以性别依赖的方式减轻TASM结扎后的持续性疼痛,(2)大鼠三叉神经节(TG)中莫尔表达变化是否存在性别差异。莫尔激动剂,D-Ala 2,N-Me-Phe 4,Gly 5-ol]-脑啡肽乙酸盐(DAMGO),在雄性、雌性和双侧睾丸切除(GDX)雄性大鼠中在TASM结扎后14天评估作用。同时测定肌腱结扎后14天TG中莫尔mRNA和蛋白水平。结扎后3 ~ 28 d,雌雄大鼠伤侧机械阈值均显著降低。10 μg DAMGO可显著减轻雄性大鼠的触诱发痛。在雌性和GDX雄性大鼠中需要10倍更高剂量的DAMGO以产生在雄性大鼠中实现的抗异常性疼痛水平。TASM结扎后14 d,雄性大鼠TG中莫尔mRNA水平显著高于假手术组,而雌性大鼠和GDX雄性大鼠TG中MOR mRNA水平无显著差异。TASM结扎后,与假手术雄性相比,雄性TG中的莫尔免疫反应性显著更高。在接受肌腱损伤的雄性大鼠中,莫尔水平增加至假手术水平的181.8%。但雌性大鼠接受肌腱损伤相比,假手术雌性大鼠没有显着变化。以上结果提示,外周莫尔受体激动剂对TASM结扎大鼠产生持续性疼痛的作用存在性别差异,其部分原因是莫尔表达的性别差异,睾酮是调节莫尔的重要因素。
Unilateral ligation of the tendon of anterior superficial part of rat masseter muscle (TASM) leads to long-lasting allodynia. Sex differences in peripheral mu-opioid receptor (MOR)-mediated analgesia under persistent myogenic pain are not well understood. In this study, we examined (1) whether locally applied MOR agonists attenuate persistent pain following TASM ligation in a sex dependent manner, (2) whether there are sex differences of MOR expression changes in rat trigeminal ganglia (TG). The effects of MOR agonist, D-Ala2, N–Me-Phe4, Gly5-ol]-Enkephalin acetate salt (DAMGO), were assessed 14 days after TASM ligation in male, female and orchidectomized (GDX) male rats. MOR mRNA and protein levels in TG 14 days following tendon ligation were also determined. The mechanical thresholds of the injured side were significantly decreased in both male and female rats, from 3 days to 28 days after TASM ligation. A10 μg DAMGO significantly attenuated allodynia in male rats. A 10-fold higher dose of DAMGO was required in female and GDX male rats to produce the level of anti- allodynia achieved in male rats. The level of MOR mRNA in TG from male rats was significantly greater 14 days after TASM ligation compared with the sham-operated male rats, but not from female and GDX male rats. After TASM ligation, males had significantly more MOR immunoreactivity in TG compared to sham-operated males. The MOR levels increased to 181.8% of the sham level in male rats receiving tendon injury. But there was no significant change in female rats receiving tendon injury compared to the sham female rats. Taken together, our data suggest that there were sex differences in the effects of peripheral MOR agonists between male and female rats under TASM ligation developing long-lasting pain condition, which is partly mediated by sex differences in the changes of MOR expressions and testosterone is an important factor in the regulation of MOR.
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发表时间: 2011-08
期刊: STEM CELLS
影响因子: 5.2
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