摘要
目的:研究骨癌痛大鼠脊髓背角广动力范围(wide dynamic range,WDR)神经元兴奋性的改变,探讨KCNQ/M(Kv7)钾通道在骨癌痛中枢敏化中的作用。方法:在雌性SD大鼠,采用胫骨骨髓腔内注射MRMT-1乳腺癌细胞(4×104,4μl)的方法建立骨癌痛大鼠模型,术后14天用von Frey纤维丝测定大鼠同侧后爪的50%缩足阈值(paw withdrawal threshold,PWT)以检测造模是否成功。对照组注射等体积的磷酸盐缓冲液(PBS组)。造模后14天,通过在体细胞外记录的电生理学方法,观察造模前后脊髓背角WDR神经元的放电变化以及脊髓背表面给予KCNQ钾通道的激动剂瑞替加滨(retigabine,RTG)5 mM对骨癌痛大鼠脊髓背角WDR神经元C-纤维诱发放电的影响。结果:建立模型后14天,(1)与PBS组相比,模型组WDR神经元的C-纤维诱发放电明显增多(P<0.001,n=11);(2)与DMSO组相比,脊髓背表面给予瑞替加滨可以显著抑制骨癌痛大鼠WDR神经元的C-纤维诱发放电(P<0.001,n=14)。结论:骨癌大鼠脊髓背角WDR神经元的兴奋性显著升高(即发生了中枢敏化);KCNQ/M(Kv7)钾通道的功能性下调可能与骨癌大鼠的中枢敏化和骨癌痛的发生有关。
Objective： To investigate the excitabilities of spinal wide dynamic range （WDR） neurons in a rat model of bone cancer pain, and to explore the role of KCNQ/M （Kv7） potassium channels in the development of central sensitization in bone cancer rats. Methods： （1） A rat model of bone cancer pain was established by intratibial injections of syngeneic MRMT-1 mammary gland carcinoma ceils （4 ~ 104, 4 ~tl） in female Sprague- Dawley rats. The 50% paw withdrawal threShold （PWT） of rats were tested with von Frey filaments on 14 days after cancer cells inoculation to assess the mechanical allodynia, which indicated the success of bone cancer painmodel. An equal volume of vehicle （phosphorylated buffer solution, PBS）was injected into the tibial bone caviiy as controls. （2） The alterations of excitabilities of WDR neurons in bone cancer pain rats and the effects of retigabine on the C-fiber induced discharge of spinal wide dynamic range （WDR） neurons were examined through extraceUular electrophysiological recording in vivo in bone cancer pain rats. Results： （1） The C-fiber responses of WDR neurons increased significantly in rats with bone cancer pain （P 〈 0.001, n = 11）; （2） Spinal administration ofretigabine （5 mM）, a selective opener of KCNQ/M （Kv7） channels, showed significant inhibition on the C-fiber evoked discharges of dorsal hom WDR neurons （P 〈 0.001, n = 14）. Conclusion： Hypersensitivity of dorsal horn WDR neurons occurs in rats with bone cancer pain, which is highly related to the central sensitization and the pathogenesis of bone cancer pain. KCNQ/M （Kv7） potassium channels may underlie the occurrence of central sensitization and the development of bone cancer pain in rats.
出处
《中国疼痛医学杂志》
CAS
CSCD
北大核心
2014年第2期108-112,共5页
Chinese Journal of Pain Medicine
基金
国家自然科学基金(81371237,31171063)
科技部国家重点基础研究发展计划“973”资助项目(2013CB531905)
卫生部行业专项基金(201302013-01)
北京市自然科学基金(7112079)资助
