鞘内注射氯沙坦减少腓肠肌切口痛模型大鼠痛敏

Intrathecal losartan reduced pain threshold in gastrocnemius incision pain rats model

目的观察鞘内注射不同剂量氯沙坦对腓肠肌切口痛模型大鼠痛阈的影响。方法选用鞘内置管后建立大鼠行腓肠肌切口疼痛模型,随机分为鞘内3种剂量注射氯沙坦组[Losartan 0.1 nmol(IL1组)、Losartan 1 nmol(IL2组)、Losartan 10 nmol(IL3组)]和生理盐水对照组(IS组)、非切口痛鞘内置管对照组(sham组),每组各6只。在建立腓肠肌切口痛模型后1 d鞘内给药,观测各组大鼠造模前、造模后3 h、鞘内注射前2 h(T_0)、鞘内注射后1 h(T_1)、2 h(T_2)、6 h(T_3)和1 d(T_4)各时间点的前后大鼠右足底机械痛阈和热痛阈值。结果与造模前比较,各组大鼠造模后3 h机械痛阈和热痛阈值均明显降低(P<0.01)。大鼠鞘内注射不同浓度氯沙坦后,在给药干预后不同时间,各组内机械触诱发痛阈(MWT)(P<0.01)和热缩腿反射潜伏期(PTWL)不全相同(P<0.01);给药干预后同一时间,各组间MWT(P<0.01)和PTWL不全相同(P<0.01);与T_0时比,T_1、T_2和T_3时鞘内注射氯沙坦后MWT及PTWL增高并与剂量有关。结论鞘内注射氯沙坦可以减轻切口痛模型大鼠痛敏并与剂量相关。

Objective To investigate the effects of intrathecal administration of losartan on pain thresholds in gastrocnemius incision pain rats model. Methods Thirty male Sprague-Dawley rats with intrathal cannulae were used in this study. Rats were randomized to five groups [Losartan 0. 1 nmol（ group IL1）,Losartan 1 nmol（ group IL2）,Losartan 10 nmol（ group IL3） and saline（ group IS） ],and sham as control（ group sham）,six in each group. Mechanical paw withdrawal threshold（ MWT） to von Frey filament stimulation and potential thermal withdraw latency（ PTWL） were measured before and at 3 h after incision,as well as 2 h（ T0） before intrathercal injection,1 h（ T1）,2 h（ T2）,6 h（ T3） and 1 d（ T4） after intrathercal injection. Results Two-way repeated-measures ANOVA revealed significant differences of the time on MWT（ P〈0. 01） and PTWL（ P〈0. 01） among groups. There were significant difference on MWT and PTWL between groups at the same time point after intrathecal drugs administration（ P〈0. 01）. Compared with time T0,MWT and PTWL in time T1,T2 and T3 increased in dose-dependent fashion after intrathercal injection of losartan. There is interactions between different doses of losartan intervention and time. Conclusion The hyperalgesia behaviors of rats with gastrocnemius incision was inhibited in a dose-dependent fashion by intrathecal administration of losartan.