卢非酰胺选择性抑制大鼠C纤维介导的伤害性初级传入发挥镇痛作用  

Rufinamide plays the anti-allodynia role via selectively inhibiting C-fiber mediated nociceptive primary afferents in rats

作　　者：刘洁[1] 白晓光[1] 刘暾[1] 李建民[1] 王群[1] 濮雅楠 吕岩[1] 

机构地区：[1]第四军医大学西京医院麻醉科,西安710032

出　　处：《神经解剖学杂志》2015年第2期131-137,共7页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(81471139);陕西省社会发展科技攻关项目(2012SF2-04-01)

摘　　要：目的:探讨抗癫痫药物卢非酰胺(rufinamide,RUF)对脊髓背角II层胶状质(substantia gelatinosa,SG)神经元兴奋性和突触传递的影响及其在神经病理性疼痛动物模型上的镇痛作用。方法:利用膜片钳技术,对SG神经元进行全细胞记录,观察卢非酰胺对神经元动作电位(action potentials,AP)发放频率及后根刺激诱发的兴奋性突触后电流(evoked excitatory postsynaptic currents,e EPSC)幅度及自发性兴奋性突触后电流(spontaneous excitatory postsynaptic currents,s EPSC)的影响。制备大鼠腰5脊神经结扎模型(spinal nerve ligation,SNL),观察腹腔注射卢非酰胺对机械性缩足反射阈值(paw withdrawal mechanical threshold,PWMT)的影响。结果:电生理结果显示:灌注卢非酰胺可明显抑制由C纤维介导的单突触e EPSC幅值,这一作用经洗脱可恢复至加药前,但对Aδ纤维介导的e EPSC幅度的抑制作用无统计学意义。卢非酰胺还可减少II层胶状质神经元动作电位的发放频率,减弱神经元的兴奋性,同时降低s EPSC的频率,但对其幅度没有影响。在大鼠SNL模型上,卢非酰胺能有效缓解由神经结扎引起的病理性疼痛,且镇痛作用具有浓度依赖性。结论:卢非酰胺可以通过减少SG神经元动作电位的发放频率,选择性的抑制脊髓背角浅层C纤维介导的伤害性初级传入而发挥镇痛作用。Objective： To examine the influence of rufinamide on neuronal excitability and synaptic transmission in spinal substantia gelatinosa（ SG）,meanwhile,explore the anti-allodynia effects in neuropathic pain model rats. Methods：Whole-cell,voltage-clamp recordings were made in SG neurons to investigate the effect of rufinamide on action potentials（ APs） of SG neurons,dorsal root stimulation evoked excitatory postsynaptic currents（ e EPSCs） and spontaneous excitatory postsynaptic currents（ s EPSCs）. The paw withdrawal mechanical threshold（ PWMT） was measured on spinal nerve ligation（ SNL） neuropathic pain model to examine the effects of rufinamide. Results： The electrophysiological studies showed that rufinamide significantly inhibited the peak amplitude of monosynaptic e EPSCs mediated by primary C fibers,but had little effect,if any,on Aδ fiber mediated e EPSCs. Rufinamide also significantly inhibited the frequency of APs in SG neurons. The frequency of s EPSCs in SG neurons was decreased by the superfusion of rufinamide,while the amplitude of s EPSCs was not affected. Rufinamide could effectively alleviate neuropathic pain caused by nerve ligation,furthermore,this effect exhibited dose-dependent. Conclusion： Rufinamide contributes to anti-allodynia effects by inhibiting the pri-mary C-fiber mediated synaptic transmission and excitability of SG neurons in rats.

关 键 词：卢非酰胺 神经病理性疼痛 膜片钳 脊髓胶状质 兴奋性突触后电流 大鼠 

分 类 号：R614[医药卫生—麻醉学]