鞘内注射米诺环素对皮肤／肌肉切口和牵拉术后持续性痛大鼠机械缩足反射阈值的影响

Effects of intrathecal minocycline on MWT in a rat model of SMIR-evoked persistent postoperative pain

目的研究鞘内注射小胶质细胞活化特异性抑制剂米诺环素对皮肤／肌肉切口和牵拉（skin／muscle incision and retraction，SMIR）术后持续性痛大鼠机械缩足反射阈值（mechanical withdrawal threshold，MWT）的影响。方法选择鞘内置管成功的雄性SD大鼠32只，按随机数字表随机分为4组（每组8只）：正常对照组、假手术组、SMIR模型组和SMIR模型±米诺环素组（简称米诺环素组）。按Yaksh法鞘内置管；按Flatters法制作大鼠SMIR术后持续性痛模型；应用vonFrey纤维细丝法测定MWT来评定疼痛行为学变化。结果与术前基础值和正常对照组比较，假手术组各时间点的MWT均无明显变化（术前基础值为13．0±0．9，正常对照组和假手术组在术前及术后第1、3,7、12、22、32天的MWT分别为13．2±0．9和13．0±0．9，13．2±0．7和12．9±1．0，12．9±0．8和12．7±1．1，12．8±1．2和13．0±1．0，13．3±0．7和13．2±1．0，12．8±0．8和12．9±1．2，12．9±1．1和13．1±0．8，P〉0．05）；与术前基础值和假手术组相应时间点比较，SMIR模型组在术后第3、7、12、22天的MWT均明显下降（术前基础值为13．1±0．8，假手术组和SMIR模型组在术后第3、7、12、22天的MWT分别为12．7±1．1和9．1±0．3，13．0±1．0和7．8±1．0，13．2±1．0和5．4±1．0，12．9±1．2和9．0±0．4。P〈0．05）；与SMIR模型组相应时间点比较，米诺环素组在术后第3、7、12、22天的MWT明显增加（SMIR模型组和米诺环素组术后第3、7、12、22天的MWT分别为9．1±0．3和10．8±1．3，7．8±1．0和8．9±0．1，5．4±1．0和8．0±1．1，9．0±0．4和9．9±0．7，P〈0．05）。结论在大鼠SMIR术后持续性痛模型中，鞘内注射米诺环素可明显减轻SMIR引起的疼痛行为学变化，提示脊髓小胶质细胞的活化在术后持续性痛发生和发展中具有重要作用。

objective To observe the effects of intrathecal minocycline （a selective inhibitor of microglia activation） on mechanical withdrawal threshold （MWT） in a rat model of persistent postoperative pain evoked by skin/muscle incision and retraction （SMIR）. Methods 32 male Sprague-Dawley rats were randomly divided into four groups according to random number table （n=8）： normal control group, sham operation group, SMIR model group and SMIR model plus intrathecal minocycline group （minocycline group）. A PE-10 catheter was inserted into the subarachnoid space（intrathecal） according to the method described by Yaksh et al. A rat model of persistent postoperative pain evoked by SMIR was made according to the method described by Flatters. Pain behavior was assessed by MWT to von Frey filament stimulation intensity. Results Compared with both preoperative baseline and normal control group, the MWT of sham operation group did not change significantly at each time point （preoperative baseline： 13.0±0.9, the MWT of normal control group and sham operation group before operation and at postoperative days 1, 3, 7, 12, 22 and 32 were 13.2±0.9 and 13.0±0.9, 13.2±0.7 and 12.9±1.0, 12.9±0.8 and 12.7±1.1, 12.8±1.2 and 13.0±1.0, 13.3±0.7 and 13.2±1.0, 12.8±0.8 and 12.9±1.2, 12.9±1.1 and 13.1±0.8, respectively, P〉0.05）. However, compared with both preoperative baseline and sham operation group, the MWT of SMIR model group decreased significantly at postoperative days 3, 7, 12 and 22 （preoperative baseline： 13.1±0.8, the MWT of sham operation group and SMIR model group at postoperative days 3, 7, 12 and 22 were 12.7±1.1 and 9.1±0.3, 13.0±1.0 and 7.8±1.0, 13.2±1.0 and 5,4±1.0, 12.9±1.2 and 9.0±0.4, respectively, P〈0.05）; Compared with SMIR model group, the MWT of minocycline group increased significantly at postoperative days 3, 7, 12 and 22 （the MWT of SMIR model group and minocyeline group at postoperative （lays 3, 7, 12 and 22 were 9.1±0.3 and 10.8±1.3, 7.8±1.0 and 8.9±0.1, 5.4±1.0 and 8.0±1.1, 9.0±0.4 and 9.9 ±0.7, respectively, P〈0.05）. Conclusion Intratheeal minocyeline markedly attenuates pain symptoms in a rat model of persistent postoperative pain evoked by SMIR, which suggests development and maintenance of persistent postoperative pain.