川芎嗪对神经病理性疼痛模型大鼠的镇痛作用及对脑中枢敏化区氨基酸类神经递质含量的影响

Effect of ligustrazine on analgesic effect and amino acid transmitters in central sensitizations of brain regions in neuropathic pain model rats

目的研究川芎嗪对坐骨神经部分损伤(SSNI)诱导的神经病理性疼痛模型大鼠痛敏行为的作用,并探讨其对脑腹内侧前额叶皮质(m PFC)和杏仁核中央核(Ce A)细胞外液中氨基酸类神经递质含量的影响。方法雄性SD大鼠,随机分为假手术组、SSNI模型组和川芎嗪组,分别通过丘脑腹后外侧核(VPLNT,2.5μmol·kg^(-1))、鞘内(it,25μmol·kg^(-1))和静脉(iv,20 mg·kg^(-1))注射给予川芎嗪或生理盐水。采用纤维丝机械刺激法和冷喷法评价大鼠机械痛敏和冷痛敏行为。应用颅内双位点同步微透析采集mPFC和CeA细胞外液,高效液相-荧光色谱法检测细胞外液中谷氨酸(Glu)、天冬氨酸(Asp)、甘氨酸(Gly)和γ-氨基丁酸(GABA)的含量。结果与假手术组相比,SSNI模型组大鼠机械痛阈值显著降低(P<0.01),冷痛敏评分显著升高(P<0.01),mPFC细胞外液中Glu和Gly及CeA细胞外液中Gly含量均显著升高(P<0.05,P<0.01)。与SSNI模型组相比,iv注射川芎嗪(20 mg·kg^(-1))能明显升高SSNI模型大鼠的机械痛阈和降低冷痛敏评分(P<0.05);VPLNT,it和iv注射川芎嗪能显著降低SSNI模型大鼠mPFC细胞外液中Glu,Asp和Gly以及CeA细胞外液中Glu和Gly含量(P<0.05,P<0.01)。结论川芎嗪的镇痛作用可能与其抑制大鼠脑mPFC和CeA内兴奋性氨基酸递质Glu和Gly的释放、调控兴奋性和抑制性氨基酸类神经递质的动态平衡及缓解Glu兴奋性毒性造成的中枢敏化效应有关。

OBJECTIVE To study the effect of ligustrazine(Lig)on the pain-sensitive behaviors and the concentrations of excitatory amino acid transmitters in the extracellular fluid of the medial prefrontal cortex(mPFC)and central nucleus of the amygdaloid(CeA)in neuropathic pain model rats induced by spared sciatic nerve injury(SSNI).METHODS Male SD rats were randomly divided into sham,SSNI model,and Lig groups.Rats in Lig groups were given Lig 2.5μmol·kg-1through the ventral posterior lateral nucleus of the thalamus(VPLNT),25μmol·kg-1through intrathecal(it),20 mg·kg-1through intravenous(iv)injections,respectively.The mechanical withdraw threshold and cold spray scores were evaluated by von Frey hairs and cold spray for the pain-sensitive behaviors.Dialysis samples of the extracellular fluid of mPFC and CeA were collected synchronously by the intracranial double-probe microdialysis,and the concentrations of glutamate(Glu),aspartic acid(Asp),glycine(Gly)andγ-aminobutyric acid(GABA)were measured by the high performance liquid chromatography-fluorescence detector.RESULTS Compared with sham group,the mechanical withdraw threshold was significantly decreased(P<0.01),and cold spray scores were significantly increased(P<0.01)in the SSNI model rats.The levels of Glu and Gly in extracellular fluids of mPFC,and the level of Gly in extracellular fluids of CeA were significantly increased in SSNI model rats(P<0.05,P<0.01).Compared with the SSNI model rats,Lig 20 mg·kg-1by iv injections could significantly increase the mechanical withdraw threshold and decrease the cold spray scores(P<0.05).Lig given through VPLNT,it and iv injections also decreased the levels of Glu,Asp and Gly in the extracellular fluids of m PFC,and Glu and Gly in the extracellular fluids of Ce A in SSNI rats(P<0.05,P<0.01).CONCLUSION The analgesic effect of Lig may be related to the inhibition of excitatory amino acid transmitters(Glu and Gly)release with brain regions in the SSNI rats,the regulation of the dynamic balance of excitatory and to inhibitory amino acid neurotransmitters,and the protection of the central sensitization effect induced by excitatory toxicity of Glu.