目的 探讨三叉神经颈髓复合体内缝隙连接蛋白43(Cx43)对偏头痛大鼠痛觉超敏的影响. 方法 将SD大鼠随机数字表法分为空白组、假手术组、生理盐水组、改良致炎剂3d组、改良致炎剂7d组、甘珀酸(CBX)预防组、CBX预防对照组、CBX治疗组和CBX治疗对照组,每组6只.用改良致炎剂反复刺激硬脑膜法建立偏头痛大鼠模型.Von-Frey纤维丝测定眶周痛觉阈值,免疫荧光染色法观察大鼠三叉神经颈髓复合体内Cx43的表达. 结果 行为学结果显示,与对照组相比,改良致炎剂组大鼠眶周痛阈逐日下降,出现痛觉超敏表现;而CBX预防组大鼠未出现痛觉超敏表现;CBX治疗组大鼠给予CBX后痛阈上升.细胞核及Cx43免疫荧光染色显示:改良致炎剂组大鼠后角细胞数及Cx43表达较对照组增多,3d组以Ⅰ、Ⅱ层增多为主,7d组以Ⅰ~Ⅳ层增多为主;CBX预防组及治疗组Cx43平均吸光度值与其对照组相比,差异有统计学意义(P<0.05). 结论 反复予硬脑膜改良致炎剂能有效诱导偏头痛大鼠产生眶周痛觉超敏表现,并能引起三叉神经颈髓复合体内Cx43表达上调.非特异性缝隙连接阻断剂CBX能有效抑制Cx43表达上调,缓解痛觉超敏,提示Cx43在偏头痛大鼠痛觉超敏形成和加重中起重要作用.
Objective To investigate the efficacy of connexin43 (Cx43) in trigeminocervical complex on allodynia in rat models of migraine.Methods SD rats were randomly divided into 9 groups (n=6):blank group,sham-operated group,saline group,improved inflammatory soup for 3 d group,improved inflammatory soup for 7 d group,carbenoxolone (CBX) prevention group,CBX prevention control group,CBX treatment group and CBX treatment control group.Improved inflammatory soup was used to stimulate the dual matter adjacent to the superior sagittal sinus of rats repeatedly to induce migraine models in the later 7 groups.The pain threshold of periorbital skin was measured by Von-Frey hairs.On the 11th postoperative day,the spinal cord was removed for detection of Cx43 expression in the trigeminocervical complex by immunofluorescence.Results Von-Frey hairs study showed that:the pain threshold of improved inflammatory soup groups had a daily drop; rats in the improved inflammatory soup for 3 d group suffered allodynia,while those in the CBX prevention group did not; the pain threshold in the CBX treatment group ascended after using CBX.Immunofluorescence of nucleus and Cx43 showed that:the mean optical density (OD) of improved inflammatory soup for 3 d group and for 7 d group significantly incresed (P〈0.05); nucleus and Cx43 abundantly expressed in lamina Ⅰ and Ⅱ of dorsal horn in the improved inflammatory soup for 3 d group and lamina Ⅰ-Ⅳ of dorsal horn in improved inflammatory soup for 7 d group; significant difference was noted on the mean OD values between of CBX prevention/treatment groups and their control groups (P〈0.05).Conclusion Repeatedly infusing improved inflammatory soup to dual matter can effectively induce allodynia in rat models of migraine and Cx43 abundantly expresses in trigeminocervical complex after being given the soup; allodynia in migraine model of rats can be prevented and relieved by intraperitoneal administrating of CBX,which suggests that Cx43 may play an important role i