鞘内单次注射吗啡对神经病理痛大鼠脊髓背角CGRP表达的影响

EFFECTS OF INTRATHECAL MORPHINE ON CHANGES OF NEURONAL CGRP EXPRESSION IN SPINAL DORSAL HORN IN RATS WITH NEUROPATHIC PAIN

目的：观察鞘内单次注射吗啡对神经病理痛大鼠脊髓背角降钙素基因相关肽（Calcitoningene-related peptide CGRP）表达的影响。方法：20只健康雄性SD大鼠,体重200-270 g,随机分为4组：对照组（C组,n=5）,假手术组（S组,n=5）,生理盐水组（N组,n=5）,吗啡组（M组,n=5）。C组不做任何处理,其它3组均根据改良Yaksh法进行鞘内置管;N组和M组制备神经病理痛模型（SNI模型）,制模2 d后,N组和M组分别鞘内注射生理盐水和吗啡10μg,容量为20μ。l每组均在SNI术前1d（基础值）到术后2d内每天测定机械痛阈和热缩足潜伏期,并全部在注药后2h处死大鼠,用免疫组织化学方法观察大鼠L5节段水平脊髓背角CGRP的表达。结果：与C组和S组比较,N组机械痛阈降低,CGRP表达上调（P〈0.05）,热缩足潜伏期差异无统计学意义（P〉0.05）。与N组比较,M组机械痛阈升高,热缩足潜伏期延长,CGRP表达下调（P〈0.05）。结论：鞘内单次注射吗啡对神经病理痛大鼠在产生镇痛效应时引起脊髓背角CGRP表达下调。

Objective：To investigate the effect of intrathecal morphine on changes of neuronal CGRP expression in the spinal dorsal horn in rats with neuropathic pain. Methods： Twenty healthy male Sprague - Dawley rats （200 -270 g） were randomly divided into four groups （n = 5 ） ： control group （group C）, sham group （group S）, normal saline group （ group N） and morphine group （group M）. Both group N and group M were received a lesion to two of the three terminal branches of the sciatic nerve （ tibial and common peroneal nerves） leaving the remaining sural nerve intact （spared nerve injury model, SNI）. The rats in group M were intrathecally injected 10 μl morphine （ 10 μg） followed by 10 μl normal saline 1 time at 2 days post-surgery, rats in group N were intrathecally injected 20 μl normal saline in uniform interval. Pain behaviours were measured on day 1 pre-surgery and on day 1,2 post-surgery after intrathecally injection. The rats in four groups were killed 2 hours after intrathecal injection, and the expression of CGRP in the spinal dorsal horn of L5 segment were determined using immunohistochemistry. Results： Compared with group C and group S, mechanical allodynia threshold in group N was decreased on day 2 post-surgery （ P 〈 0. 05 ）, and the expression of CGRP immunoreactive soma in the superficial laminae of the L5 spinal dorsal horn in group N was significantly increased （ P 〈 0.05 ）, but there was no significant difference in the radiant heat stimulus paw withdrawal latency （P 〉 0.05 ）. Mechanical stimulation pain threshold was elevated and radiant heat stimulus paw withdrawal latency was prolonged in group M compared with group N, and the expression of CGRP immunoreactive soma in the superficial laminae of the L5 spinal dorsal horn in group M decreased significantly on day 2 postsurgery compared with group N （P 〈 0.05 ）. Conclusion ： Intrathecal administration of morphine can provide significant antinociception in rats with neuropathic pain, and its inhibition of CGRP is involved in the antinociception mechanism.