离子型及Ⅰ型代谢型谷氨酸受体对大鼠温度过敏的调节作用

摘要

目的 探讨离子型及Ⅰ型代谢型谷氨酸受体对大鼠温度过敏的调节作用.方法 将离子型谷氨酸受体作用药谷氨酸(Glu)、N-甲基-D-天冬氨酸(NMDA)、α-氨基-3羟基-5甲基-4异恶唑(AMPA),Ⅰ型代谢型谷氨酸受体作用药[(S)-DHPG],非竞争性NMDA受体拮抗剂(MK-801),竞争性AMPA受体拮抗剂(CNQX),选择性Ⅰ型代谢型谷氨酸受体拮抗剂(cpccoEt)分别注入L5～6脊神经结扎和假手术大鼠左足底部皮下组织,观察大鼠对辐射热的反应.结果 Glu、NMDA、AMPA、(S)-DHPG能减少假手术组足底逃避阈值,而对手术组则无效;相反,MK-801、CNQX及cpccoEt 能增加手术组足底逃避阈值,但对假手术组无效.结论 外周离子型和Ⅰ型代谢型谷氨酸受体敏感性的改变可导致末梢神经可塑性变化,这种变化是神经损伤引发的神经病理性疼痛产生与维持的基础.%Objective To study the effects of ionic and group Ⅰ metabotropic glutamate receptors on rats' thermal hypersensitivity by intraplantar administration of drugs. Methods After intraplantar administration of glutamate receptor agonists,L-glutamic acid (Glu), N-methyl-D-aspartic-acid (NMDA),and (RS)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid hydrobromide (AMPA);a Group Ⅰ mGluR agonist, (S) 3,5-dihydroxyphenylglycine [(S)-DHPG];a noncompetitive NMDA receptor antagonist, (+)-MK801 maleate (MK-801);a competitive AMPA/kainate receptor antagonist,6-cyano-7-nitroquinoxaline-2,3-dione (CNQX);and a selective GroupⅠ mGluR antagonist,7-hydroxyiminocyclo propan[b]chromen-1a- carboxylic acid ethyl ester (cpccoEt) into the left hind paws of rats whose L5-6 nerves were sham-operated or ligated,we examined the response of the rats to thermal stimuli provided by radiant heat. Results In sham-operated rats,glutamate,NMDA,AMPA,and (S)-DHPG reduced paw withdrawal latency (PWL) but did not have any effect on SNL rats. However,in SNL rats,MK-801,CNQX,and cpccoEt increased PWL but exerted no effect on sham-operated rats. Conclusion These results suggest that changes in sensitivity of peripheral ionic and group Ⅰ metabotropic glutamate receptors can lead to changes in peripheral nerve plasticity;the generation and maintenance of neuropathic pain caused by nerve injury is based on this plasticity.