神经痛大鼠痛行为与ω-芋螺毒素SO3的影响

Effects of omega-conotoxin SO3 on pain related behaviors of rats with neuropathic pain

目的:有研究显示ω-芋螺毒素SO3与SNX-111结构相似,探讨蛛网膜下腔注射ω-芋螺毒素SO3或SNX-111对慢性压迫性损伤后神经痛的大鼠痛行为的影响。方法:实验于2004-02/07在军事医学科学院生物工程研究所蛋白质工程室及实验动物中心完成。采用随机对照双盲法。制备右侧坐骨神经慢性挤压伤模型并行蛛网膜下腔置管成功的雄性SD大鼠90只,随机均分为9组。对照组经导管鞘内注射生理盐水20μL,其余8组动物分别经导管鞘内注射SO3或SNX-111300,600,900和1200ng。观察各组动物坐骨神经结扎前、给药前、给药后每隔1h热痛觉过敏及触觉异常的反应阈值。各毒素不同剂量给药后2h与给药前阈值比较采用配对t检验;两种毒素相应剂量间的比较采用t检验。结果:两种毒素均呈剂量依赖性提高坐骨神经慢性挤压伤大鼠热刺激痛及触诱发痛阈值。鞘内注射SO31200ng2h后热痛阈最大可能镇痛百分率达94%,触诱发痛阈值也由给药前的2.94g上升到9.20g。结论:蛛网膜下腔注射SO3可有效地治疗神经源性疼痛,其镇痛作用与剂量相关,镇痛强度与SNX-111相近。

AIM:It has been studied that ω conotoxin SO3 and SNX 111 are similar in the ir structure.In this study,we investigated the effects of ω conotoxin SO3 or S NX 111 through subarachnoid injection on pain related behaviors in rats with ne uropathic pain induced by chronic constriction injury(CCI). METHODS:The experiment was conducted in the Department of Protein Engineering and Center for Experimental Animals in the Institute of Biotechnology,Chinese Ac ademy of Military Medical Sciences from February to July 2004.A randomized contr olled,double blind method was used.Ninety SD rats were established into models of right sciatic nerve CCI and implanted with chronic lumbar subarachnoid cathet ers.They were randomly divided into 9 groups of 10 animals each.In the control g roup,the animals were intrathecally injected with normal saline 20 μL,and the a nimals in other 8 groups with SO3 or SNX 111 300,600,900 and 1 200 ng(in 20 μL normal saline) respectively.Hyperalgesia and paraesthesia allodynia of the anim als were tested by measuring paw withdrawal latency(PWL) in response to thermal stimulation and von Frey filaments before deligation,before administration,ever y 1 hour after administration.The threshold before administration and 2 hours af ter administration of SO3 or SNX 111 with different doses was compared by t tes ts,and the corresponding doses of SO3 and SNX 111 data were compared by t tests . RESULTS:The threshold values of thermal and tactile allodynia were both increa sed in the sciatic nerves of rats with CCI after administration of SO3 or SNX 1 11 in a dose dependent manner.The maximum analgesia rate of thermal allodynia r eached 94%2 hours after intrathecal injection of SO3 1200 ng,and meanwhile,the threshold values of tactile allodynia were decreased from 2.94 g before administ ration to 9.20 g after administration. CONCLUSION:Subarachnoid injection of SO3 is antinociceptive effectively in a d ose dependent manner in a rat CCI model of neuropathic pain,and the effects are similar to those by subarachnoid injection of SNX 111.