鞘内注射米诺四环素对慢性坐骨神经结扎大鼠机械痛敏和热痛敏的影响

目的观察鞘内注射小胶质细胞抑制剂米诺四环素对慢性坐骨神经结扎大鼠机械痛敏和热痛敏的影响。方法所有大鼠术前8d鞘内置管,用机械缩足反射阈值和热缩足潜伏期来分别评价大鼠机械痛敏和热痛敏。前给药组:生理盐水10μl或米诺四环素50μg,于坐骨神经结扎前1d开始持续到术后1d(每天2次)鞘内注射,机械缩足反射阈值和热缩足潜伏期分别于术前2d,术后1,3,5,7,14d测定;后给药组:坐骨神经结扎后7d,鞘内注射1次生理盐水10μl或米诺四环素50μg,其对机械缩足反射阈值和热缩足潜伏期的影响分别于给药后0.5、1、2、4、8h测定。结果CCI大鼠从术后1d形成稳定的热痛敏和机械痛敏,前鞘内注射米诺四环素明显增加CCI大鼠MWT和TWL(P<0.05,P<0.01),相反,后鞘内注射米诺四环素对CCI大鼠MWT和TWL无明显影响。结论前鞘内注射米诺四环素明显抑制CCI大鼠机械痛敏和热痛敏,提示小胶质细胞的活化参与慢性坐骨神经结扎引发神经病理痛的形成。

Intrathecally administration of minocycline on mechanical allodynia and heat hyperalgesia induced by chronic constriction injury of the sciatic nerve in rats

Aim To observe the effect of intrathecal minocycline ,a microglial inhibitor,on mechanical allodynia and heat hyperalgesia induced by chronic constriction injury(CCI) of the sciatic nerve in rats. Methods Rats in all groups were intrathecally cathetered at 8 d before operation. Mechanical allodynia and heat hyperalgesia were evaluated by mechanical withdrawal threshold(MWT) and thermal withdrawal latency(TWL),respectively. In a preemptive treatment group,normal saline(10 μl) or minocycline (50 μg), beginning on 1 day before surgery, were administered twice daily for 3 days, the TWL and MWT were measured before surgery and on days 1,3,5,7 and 14 after surgery; in post-surgery treatment group,The effect of minocycline or saline on TWL and MWT was examined at 0.5,1,2,4,and 8 h after its intrathecal administration initiated on day 7 after surgery. Results CCI group formed steady mechanical allodynia and heat hyperalgeia from the first day after surgery to the end of this study. Preemptive administration of minocycline evidently increased the CCI rats MWT and TWL, on the contrary, initiation of minocycline treatment to rats after day 7 of nerve injury did not show any significant effect on the MWT and TWL compared with vehicle-treated nerve-injured rats. Conclusion Preemptive treatment with minocycline remarkably suppressed mechanical allodynia and heat hyperalgesia of rats following CCI,suggesting microglial activation is involved in the development of neuropathic pain induced by chronic constriction injury (CCI).