Objective To observe the effects and time-effect relationship of Koumine on evoked pain induced peripheral nerve injury ,and to investigate w hether the spinal cord is the site of action of Kou-mine . Methods Effects of repeated subcutaneous administration of Koumine (0 .28 and 7 .0 mg/kg , twice per day ,on day 3 to day 9 post-operation) on evoked neuropathic pain were observed on rat chronic constriction injury (CCI) model by thermal hyperalgesia . Effects and time-effect relationship of a single subcutaneous administration of 7 .0 mg/kg Koumine on evoked neuropathic pain were observed at 0 .5 ,1 , 2 ,4 and 6 h post-dose on rat CCI model by thermal hyperalgesia . T he 50% effective doses (ED50 ) of Koumine on evoked neuropathic pain ,for a single subcutaneous and intrathecal administration respective-ly ,were measured by Dixon’s up-and-down method to analyze whether the spinal cord is the site of action of Koumine . Results Repeated subcutaneous administration of 7 .0 mg/kg Koumine significantly re-versed thermal hyperalgesia compared to vehicle after the first administration on post-operative day 3 and reached the maximum protective effect on post-operative day 9 (reversal rate:93 .8% ,effective rate :100% ) . Single subcutaneous administration of Koumine significantly increased pain threshold relative to vehicle at 0 .5 h post-dose (reversal rate :62 .9% ,effective rate :55 .6% ) ,reached the maximum effect at 1 h post-dose (reversal rate:70 .8% ,effective rate :77 .8% ) and then decreased w hile still significantly higher than that of vehicle at 6 h post-dose . T he ED50 of Koumine by a single intrathecal administration (41 .4 μg per rat ) was far lower than that by a single subcutaneous administration (1 .074 mg/kg ) on evoked pain of CCI rats . Conclusion Koumine has a significant therapeutic effect on evoked pain induced by peripheral nerve injury . The on-set time of a single subcutaneous Koumine was within 0 .5 h and the therapeutic effect lasted for about 5 .5 h . Spinal cord might be the site of action of Koumine on neuro-pathic pain .%目的：观察钩吻素子抗外周神经损伤致神经病理性疼痛中诱发痛的效应及其时效关系，分析脊髓是否为钩吻素子抗神经病理性疼痛的可能作用部位。方法在大鼠坐骨神经慢性束缚损伤（CCI）致神经病理性疼痛模型上，以热痛觉过敏为指标，观察连续皮下注射给予钩吻素子（0．28、7．0 mg/kg ，CCI术后第3～9 d ，每天2次）对CCI大鼠诱发痛的效应；观测单次皮下注射给予7．0mg/kg钩吻素子后第0．5，1，2，4，6h对CCI大鼠诱发痛的效应及时效关系；Dixon序贯法分别测定钩吻素子皮下和鞘内注射抗CCI大鼠诱发痛作用的ED50，分析脊髓是否为钩吻素子抗神经病理性疼痛的可能作用部位。结果连续皮下注射7．0 mg/kg钩吻素子组在术后第3 d首次给药后，痛阈即显著高于溶剂对照组，术后第9 d效应最显著（翻转率为93．8％，有效率达100％）。单次皮下注射给予7．0mg/kg钩吻素子0．5h术侧足痛阈显著高于溶剂对照组（翻转率达62．9％，有效率达55．6％）；1h痛阈最高（翻转率达70．8％，有效率达77．8％），随后痛阈有所下降，但6 h仍显著高于CCI＋ saline组。单次皮下注射钩吻素子抗CCI大鼠诱发痛作用的ED50为1．074 mg/kg ，单次鞘内注射的ED50为每只41．4μg ，远低于皮下注射的ED50。结论钩吻素子具有抗外周神经损伤致神经病理性疼痛中诱发痛的效应，单次给予0．5 h内起效，持效约5．5h；脊髓可能是其发挥抗神经病理性疼痛效应的作用部位。
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