鞘内注射塞地塞米松联合螺内酯对大鼠根性神经痛行为的影响

Effects of intrathecaUy eoadministered dexamethasone and spironolactone on pain behaviors in a rat model of radicular pain

目的探讨鞘内注射地塞米松（Dex）联合螺内酯（Spir）对大鼠根性神经痛行为的影响。方法选择成功鞘内置管后无运动障碍的雄性SD大鼠48只，分为假手术组（Sham组，n=12）、溶剂对照组（C组，n=12）、Dex组（D组，n=8）、Spir组（S组，n=8）和Dex联合Spir组（Ds组，n=8），制备注射式根性神经痛模型。D组、S组和Ds组分别于造模后第2～4天，每次鞘内给予Dex4μg、Spir3μg、Dex4μg＋Spir3μg，每天2次。Sham组和C组则给予等量的10％酒精。于造模前后测量双侧足底机械缩足阈值（PWMT）和热辐射刺激潜伏期（PWTL）。结果与Sham组相比，CCD术后同侧PWMT和PWTL都明显降低（P〈0．01）。与C组相比，鞘内注射Dex明显抑制疼痛行为（P〈0．01），并一直持续到术后第10天；Spir也明显改善PWMT（P〈0．01）和PWTL（P〈0．01），并持续到术后第7天；Dex联合Spir则产生明显的协同作用[PWMT：（13．52±0．72）g，（11．58±1．38）g，P〈0．01；PWTL：（19．63±1．68）S，（14．14±1．52）S，P〈0．01]，并且这一作用持续了至少10d。结论鞘内注射Dex和Spir对慢性压迫大鼠背根神经节诱导的根性神经痛有治疗作用，二者联合使用可以产生明显的协同作用。

Objective To investigate the effects of intrathecally coadministered dexamethasone and spi- ronolactone in trathecally on radicular pain behaviors. Methods Using rat model of radicular pain induced by chronic compression of dorsal root ganglion （CCD） ,48 male SD rats successfully received intrathecal catheter implantation and without motor dysfunction were randomly divided into Sham-operation group （ Sham group, n = 12）, Control group （ C group, n = 12 ）, Dexamethasone group （ D group, n = 8 ）, Spironolactone group （ S group, n = 8 ） and Dexamethasone plus spironolactone group （DS group, n = 8 ）. Rats in D group, S group or DS group were intrathecally treated with dexamethasone 4 μg, spironolactoue 3 μg or dexamethasone 4μg plus spironolactone 3 μg twice daily on day 2 -4 after CCD respectively,while rats in C and Sham group received 10 μl 10% alcohol. Paw wiITdrawal mechanical threshold（PWMT） and paw withdrawal thermal latency （PWTL） were tested on day 1 before CCD and day 1,4,7,10,14,17 and 21 after CCD. Results Compared with Sham group, both PWMT and PWTL were significantly decreased after CCD surgery on the ipsilateral side（P〈 0.01 ）. Intrathecally administrated with dexamethasane significantly improved pain behaviors （P〈O. 01 ） and these therapeutic effects lasted up to 10 days after CCD surgery. As with dexamethasone,intrathecal spironolactone also significantly attenuated PWMT （P 〈0.01 ） and PWTL （P〈0.01） and the change lasted up to 7 days after CCD surgery. Coadministration spironolactone and dexamethasone exhibited significant synergies （ PWMT ： （ 13.52 ±0.72） g vs （ 11.58 ±1.38 ） g, P 〈 0.01;PWTL：（19.63 ± 1.68） s vs （14.14 ± 1.52） s, P〈0.01）.These effects lasted up to at least 10 days. Conclusion Both dexamethasone and spironolactone intrathecally have therapeutic effects on radicular pain behaviors, combination injection of these two drugs could generate significant synergies.