不同浓度阿米替林抗大鼠坐骨神经痛觉过敏的实验研究

PERIPHERAL ANTI-HYPERALGESIC EFFECT OF AMITRIPTYLINE FOR SCIATIC NERVE BLOCKADE ON NEUROPATHIC PAIN OF RATS

目的观察坐骨神经局部注射阿米替林对坐骨神经慢性结扎损伤(chronic constriction injury,CCI)大鼠机械和热痛阈的影响,探讨不同浓度阿米替林外周抗痛觉过敏的作用。方法健康成年雄性SD大鼠53只,体重(200±20)g,按照Bennett等的方法制备CCI模型。取模型制备成功的48只大鼠随机分为6组(n=8):NS组、A2.5组、A5组、A10组、A15.9组和Aip组。Aip组为腹腔注射阿米替林2.5mg,NS组、A2.5组、A5组、A10组和A15.9组分别于坐骨神经旁注射生理盐水0.5mL以及2.5、5.0、10.0、15.9mmol/L阿米替林0.5mL。分别于注药前及注药后1、2、4、8、12、24、48h测定大鼠机械刺激缩足反射阈值(mechanical withdrawal threshold,MWT)和热缩腿反射潜伏期(thermal withdrawal latency,TWL),并根据Hwang等运动评分进行患肢运动功能评价。结果48只大鼠均存活至实验完成,无伤口感染、肢体瘫痪及导管脱落等现象发生。A2.5组、NS组和Aip组大鼠运动功能均无明显改变,运动功能评分3组间比较差异无统计学意义(P>0.05);A5组在2h内、A10组在4h内、A15.9组在8h内均出现运动功能障碍,运动功能评分与NS组、Aip组及注药前比较,差异均有统计学意义(P<0.05);但其后运动功能均完全恢复。注药前6组大鼠MWT和TWL组间比较差异无统计学意义(P>0.05);A2.5组在2h内,A5组在4h内,A10组和A15.9组在24h内各时间点MWT及TWL较注药前、NS组和Aip组均显著升高(P<0.05),且A2.5组、A5组、A10组随阿米替林给药浓度的增加,MWT和TWL逐渐升高,持续时间逐渐延长。A15.9组与A10组间及Aip组与NS组间注药后各时间点MWT及TWL比较差异无统计学意义(P>0.05)。结论坐骨神经旁注射不同浓度(2.5～15.9mmol/L)阿米替林均可提高神经病理性疼痛大鼠的MWT和TWL,具有外周抗痛觉过敏的作用,且有浓度依赖性和封顶效应;5.0～15.9mmol/L阿米替林可产生运动阻滞,但均可完全恢复。

Objective To investigate whether the peripheral administration of hyperalgesic effect following the chronic constriction injury （CCI） of the sciatic nerve in rats amitriptyline produces anti-Methods Forty-eight male CCI rats weighing （220±20） g were randomly divided into 6 groups （n=8）： group NS, group A2.5, group A5, group A10, group A15.9 and group Aip. In the group NS, group A2.5, group A5, group A10 and group A15.9, sciatic nerve blockade was locally performed with 0.5 mL normal saline, and 2.5, 5.0, 10.0, 15.9 mmol/L amitriptyline respectively through implanted cannulas on the 7th day after operation. In the group Aip, amitriptyline （2.5 mg） was administered by intraperitoneal injection. The mechanical withdrawal threshold （MWT）, thermal withdrawal latency （TWL） and motor function were measured before and 1, 2, 4, 8, 12, 24 and 48 hours after sciatic nerve blockade. Results Forty-eight CCI rats were all survival without infection, palsy and catheter falling off. The rats of group A2.5, group NS and group Aip didn＇t produce ambulation deficits. There were no significant difference in these 3 groups （P 〉 0.05）. However compared with group A2.5, group NS and group Aip, the rats of group A5, group A10, group A15.9 all produced significant ambulation deficits （P 〈 0.05）. The ambulation deficits lasted 2 hours （group A5）, 4 hours （group A10）, 8 hours （group A159） respectively. But the ambulation deficits of CCI rats were all reversible. The MWT and TWL of groups with local injection of amitriptyline increased when conpared with group NS, group Aip and those of before injection （P 〈 0.05）. Sciatic nerve blockade with amitriptyline significantly suppressed mechanical hyperalgesia and thermal hyperalgesia in neuropathic rats. The peripheral anti-hyperalgesic effects lasted 2 hours （A2.5 group）, 4 hours （group A5）, 24 hours （group A10）, 24 hours （group A15.9） respectively. But there were no significant difference between A10 group and A15.9 group （P 〉 0.05）. There were no significant difference between group NS and group Aip （P 〉 0.05）. Conclusion The peripheral anti-hyperalgesic effects can be found in sciatic nerve blockade of amitriptyline on CCI rats. And this effect of amitriptyline has concentration dependent and ceiling effect. Amitriptyline of 5.0-15.9 mmol/L can produce significant ambulation deficits which are reversible.