大鼠口面部持续性疼痛模型中周围μ-阿片受体介导的镇痛作用的性别差异。
Sex differences in peripheral mu-opioid receptor mediated analgesia in rat orofacial persistent pain model.
作者信息
Bai Xiaofeng, Zhang Xia, Li Yanshu, Lu Li, Li Bo, He Xiaofan
机构信息
Associate Professor, Department of Oral and Maxillofacial Surgery, School & Hospital of Stomatology, China Medical University, 117 North Nanjing Street, Shenyang, P. R. of China, 110002.
Associate Professor, Department of Anesthesiology, School & Hospital of Stomatology, China Medical University, 117 North Nanjing Street, Shenyang, P. R. of China, 110002.
出版信息
PLoS One. 2015 Mar 25;10(3):e0122924. doi: 10.1371/journal.pone.0122924. eCollection 2015.
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.
大鼠咬肌前浅层肌腱（TASM）单侧结扎会导致长期的痛觉过敏。持续性肌源性疼痛下外周μ-阿片受体（MOR）介导的镇痛中的性别差异尚未完全明确。在本研究中，我们检测了：（1）局部应用MOR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MOR表达变化是否存在性别差异。在雄性、雌性和去势（GDX）雄性大鼠中，于TASM结扎14天后评估MOR激动剂[D-Ala2，N-Me-Phe4，Gly5-ol]-脑啡肽醋酸盐（DAMGO）的作用。还测定了肌腱结扎14天后TG中的MOR mRNA和蛋白水平。在TASM结扎后3天至28天，雄性和雌性大鼠受伤侧的机械阈值均显著降低。10μg DAMGO可显著减轻雄性大鼠的痛觉过敏。雌性和GDX雄性大鼠需要10倍剂量的DAMGO才能产生与雄性大鼠相同水平的抗痛觉过敏效果。与假手术雄性大鼠相比，TASM结扎14天后雄性大鼠TG中的MOR mRNA水平显著升高，但雌性和GDX雄性大鼠则不然。TASM结扎后，与假手术雄性大鼠相比，雄性大鼠TG中的MOR免疫反应性显著更高。接受肌腱损伤的雄性大鼠的MOR水平增加至假手术水平的181.8%。但与假手术雌性大鼠相比，接受肌腱损伤的雌性大鼠无显著变化。综上所述，我们的数据表明，在TASM结扎导致长期疼痛的情况下，雄性和雌性大鼠外周MOR激动剂的作用存在性别差异，这部分由MOR表达变化的性别差异介导，睾酮是MOR调节的重要因素。
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