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

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 withdrwal 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...

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

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 yon 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 minocycline group at postoperative days 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 Intrathecal minocycline markedly attenuates pain symptoms in a rat model of persistent postoperative pain evoked by SMIR, which suggests that activated spinal microglia plays an important role in the development and maintenance of persistent postoperative pain.