鞘内注射催产素对大鼠神经病理性痛的影响

Effect of intrathecal oxytocin on neuropathic pain in rats

目的本研究拟评价鞘内注射催产素对大鼠神经病理性痛的影响。方法SPF级雄性SD大鼠36只，4～6周龄，体重100～150 g，采用随机数字表法分为4组（n＝9）：对照组（C组）、神经病理性痛组（NP组）、神经病理性痛＋生理盐水组（NPN组）和神经病理性痛＋催产素组（NPO组）。NP组、NPN组和NPO组采用坐骨神经部分结扎损伤法制备神经病理性痛模型。NPO组分别于造模当天、造模后1和2 d时鞘内注射催产素10 μl（0.1 μg），然后用生理盐水10 μl冲管并封管，每天分别于9：00 a．m.和4：00 p．m.注射；NPN组于相应时点鞘内注射生理盐水20 μl并封管。分别于造模前1 d、造模后1、2、3、4、5、6和7 d时测定机械缩足反应阈（MWT）和热缩足潜伏期（TWL）。分别于造模前1 d和造模后3、7 d时采用Western blot法测定脊髓星形胶质细胞激活标记物胶质纤维酸性蛋白（GFAP）和小胶质细胞激活标记物IBa-1的表达水平。结果与C组比较，NP组和NPN组造模各时点MWT降低，TWL缩短，脊髓GFAP和IBa-1的表达上调（P〈0.05）；与NP组比较，NPN组造模后各时点MWT和TWL、脊髓GFAP和IBa-1的表达差异无统计学意义（P〉0.05）；NPO组造模后2～4 d时MWT升高，造模后1～4 d时TWL延长，造模后3 d时脊髓IBa-1表达下调，造模后3和7 d时脊髓GFAP下调（P〈0.05）。结论鞘内注射催产素可减轻大鼠神经病理性痛，其机制可能与抑制脊髓胶质细胞的激活有关。

Objective To evaluate the effect of intrathecal oxytocin on neuropathic pain in rats.Methods Thirty-six SPF male Sprague-Dawley rats, aged 4-6 weeks , weighing 100-150 g, were divided into 4 groups（n=9 each）using a random number table： control group（group C）, neuropathic pain group（group NP）, neuropathic pain plus normal saline group（group NPN）and neuropathic pain plus oxytocin group（group NPO）. The neuropathic pain model was made by partial sciatic nerve injury in NP, NPN and NPO groups.In group NPO, oxytocin 10 μl（0.1 μg）was intrathecally injected on the day of establishing the model and 1 and 2 days after establishing the model, and then normal saline 10 μl was given for tube sealing at 9 a. m.and 4 p. m.every day.In group NPN, normal saline 20 μl was given for tube sealing at the corresponding time points.The mechanical paw withdrawal threshold（MWT）and thermal paw withdrawal latency（TWL）were measured at 1 day before establishing the model and 1, 2, 3, 4, 5, 6 and 7 days after establishing the model.The expression of the astrocyte marker glial fibrillary acidic protein（GFAP）and a specific marker of microglia ionized calcium-binding adaptor molecule 1（IBa-1）was detected by Western blot at 1 day before establishing the model and 3 and 7 days after establishing the model.Results Compared with group C, the MWT was significantly decreased, TWL was shortened and the expression of GFAP and IBa-1 was up-regulated at each time point in NP and NPN groups（P〈0.05）. There was no significant difference in MWT, TWL GFAP and IBa-1 at each time point between group NPN and group NP（P〉0.05）. Compared with NP group, MWT was significantly increased at 2-4 days after establishing the model, TWL was prolonged at 1-4 days after establishing the model, the expression of IBa-1 was down-regulated on 3 days after establishing the model, and the expression of GFAP was down-regulated on 3 and 7 days after establishing the model in group NPO（P〈0.05）.Conclusion Oxytocin can reduce neuropathic pain, and the mechanism may be related to inhibiting activation of glial cells in the spinal cord of rats.