青藤碱对SSNI模型大鼠镇痛效应和纹状体细胞外液单胺类递质的影响

Analgesic effect of sinomenine on SSNI model rats and monoamine neurotransmitters in striatal extracellular fluid

目的:观察青藤碱对部分坐骨神经损伤(SSNI)诱导的神经病理性疼痛大鼠模型镇痛效应,并探讨其对纹状体细胞外液中单胺类神经递质及其代谢产物的影响。方法:雄性SD大鼠,随机分为假手术组、SSNI模型组、加巴喷丁组(100 mg.kg-1)、青藤碱高、低剂量组(40,20 mg.kg-1),采用Von Frey hairs和Cold Spray法评价机械痛敏和冷痛敏的程度。纹状体微透析采样,高效液相色谱-电化学法检测细胞外液中去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)等神经递质及其代谢产物二羟苯乙酸(DOPAC)和5-羟吲哚乙酸(5-HIAA)的含量。结果:SSNI模型大鼠的机械痛阈、冷痛敏显著改变,脑内NE显著降低,DA,5-HT及其代谢产物明显升高。与模型组相比,青藤碱高剂量组在腹腔给药30～120 min时机械痛阈显著提高(P<0.01),在30～240 min冷痛敏分值明显降低(P<0.05);在45～135 min内明显上调纹状体细胞外液NE含量(P<0.05),45,75,135 min明显降低DA的含量(P<0.05),45～135 min显著减少5-HT的含量(P<0.01),并在45～135 min显著降低DOPAC(P<0.01),45～75 min明显降低5-HIAA的含量(P<0.05)。结论:青藤碱对SSNI模型大鼠神经源性疼痛有干预作用,其机制可能与调节纹状体细胞外液单胺类神经递质紊乱相关。

Objective： To observe the analgesic effect of sinomenine on the neuropathic pain rat model induced by SSNI, and discuss its impact on monoamine neurotransmitters in striatal extracellular fluid. Method ： Male SD rats were randomly divided into the sham operation group, the SSNI model group, the gabapentin group （ 100 mg · kg-1 ）, the sinomenine high dose group （40 mg· kg- 1 ） and the sinomenine low dose group （20 mg · kg- 1 ）. Mechanical hyperalgesia and cold pain sensitivity were evaluated by Von Frey hairs and cold spray. Striatum was sampled by microdialysis. High performance liquid chromatography-electrochemical detector （HPLC-ECD） were used to detect the content of such neurotransmitters as monoamine neurotransmitters noradrenaline （NE）, dopamine （DA）, 5-hydroxy tryptamine （5-HT） and their metabolites dihydroxyphenylacetic phenylacetic acid （DOPAC） and 5-hydroxyin- doleacetic acid （5-HIAA）. Result： SSNI model rats showed significant improvement in mechanical withdrawal threshold and cold pain sensitivity, significant decrease in intracerebral NE and notable increase in DA, 5-HT and their metabolites. Compared with the model group, the sinomenine high dose group showed significant increase in mechanical withdrawal threshold at 60, 90, 180 and 240 min after abdominal administration （P 〈 0. 01 ）, significant decrease in cold pain sensitivity score during 30-240 min （P 〈 0. 05 ）. Sinomen- ine can significantly up-regulated NE content in striatal extracellular fluid during 45-135 min （P 〈0. 05 ）, remarkably reduce DA content and DOPAC at 45,75 and 135 min （P 〈0. 05）, 5-HT content during 45-135 min, DOPAC during 75-165 min （P 〈0.05 ）, and 5-HIAA during 45-135 min （P 〈0. 05）. Conclusion： Sinomenine has the intervention effect on neuropathic pain in SSNI model rats. Its mechanism may be related to disorder of monoamine neurotransmitters in striatal extracellular fluid.