6-OHDA致帕金森病大鼠模型疼痛行为学的性别差异

摘要

目的:比较6-羟基多巴胺(6-hydroxydopamine,6-OHDA)诱导帕金森病(parkinson's disease,PD)模型大鼠在疼痛发生中的性别差异,从行为学角度对比雌、雄大鼠疼痛发生的时间窗口及疼痛时程差异.方法:实验分为正常组、手术组和假手术组,每组12只大鼠(雌雄各6只).采用脑立体定位仪注射4μl 6-OHDA至成年SD大鼠黑质区(substantia nigra pars reticulata,SNr)建立PD模型.检测机械刺激缩足阈值和热刺激缩足潜伏期.结果:6-OHDA可成功复制PD并引起疼痛.正常组与假手术组无显著性的整体性别差异(机械痛敏:F=1.103,P=0.368>0.05;热痛敏:F=0.939,P=0.510>0.05).手术组机械痛敏:雌鼠术后24 h出现显著性差异,疼痛持续至56 d;雄鼠术后7 d出现显著性差异,28 d后恢复.手术组热痛敏:雌、雄大鼠发生疼痛的时间窗口与机械痛敏的时间一致.雌鼠比雄鼠疼痛时间更长(雌鼠痛持续56 d;雄鼠痛持续42 d).结论:①6-OHDA致PD模型的雌雄大鼠机械痛敏和热痛敏出现显著的整体性别差异.②雌性动物在PD中表现出更敏感、更强的痛样行为.%Objective:To compare the gender differences of 6-dopamine (6-hydroxydopamine, 6-OHDA) induced pain in rat model of Parkinson's disease (Parkinson' s disease, PD). The difference in time window of pain occurrence and pain duration between female and male rats were compared by behavioral tests.Methods:The adult Sprague-Dawley rats was divided into normal group, operation group and sham group. Each group included 12 rats (6 males and 6 females). PD model was established by Stereotaxic injection of 4 μl 6-OHDA into Substantia nigra pars reticulata (SNr). Paw withdrawal mechanical threshold and paw withdrawal thermal latency were tested in this study. Results:Stereotaxic injection of 6-OHDA successfully reproduced the PD model and caused pain behavior. There was no significant gender difference in male and female rats in normal group and sham group (mechanical allodynia :F = 1.103,P = 0.368 > 0.05; thermal hyperalgesia:F = 0.939,P = 0.510 > 0.05). The mechanical allodynia in the operation group: the female rats exhibited significant allodynia since 24 h after operation that continued to 56 d; the allodynia in male rats appeared in 7 d after operation, and recovered after 28 d. The thermal hyperalgesia in the operation group: the time window of hyperalgesia in the female and male rats was the same as that of mechanical allodynia. The female rats exhibited longer period of hyperalgesia than that of the male rats (female rats persisted 56 d; male rats persisted for 42 d).Conclusion: There are significant gender differences in mechanical allodynia and thermal hyperalgesia in male and female rats with 6-OHDA induced PD. Female animals seem to be more sensitive and more severin pain behavior in Parkinson' s disease.