右美托咪定缓解三叉神经痛小鼠动态痛觉超敏反应  

Dexmedetomidine Attenuates Dynamic Allodynia in a Mouse Model of Trigeminal Neuropathic Pain

作　　者：戚智慧 李静[1] 王钟兴[1] 胡榕 QI Zhi-hui;LI Jing;WANG Zhong-xing;HU Rong(Department of Anesthesiology,The First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China)

机构地区：[1]中山大学附属第一医院麻醉科,广东广州510080

出　　处：《中山大学学报（医学科学版）》2022年第6期898-904,共7页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(81971877);广东省区域联合基金(2020A1515110681)。

摘　　要：【目的】初步探讨右美托咪定(DEX)对三叉神经痛小鼠动态痛觉超敏反应(DA)的镇痛作用及其机制。【方法】采用松散结扎法造成左侧三叉神经分支眶下神经(ION)慢性压缩性损伤(CCI)建立三叉神经痛病理模型。C57BL/6J小鼠随机进行如下分组:Sham(假手术)组,CCI-ION组、CCI-ION+vehicle(生理盐水注射)组,CCI-ION+DEX组、Sham+DEX组,每组4~6只实验动物。CCI-ION 7 d后,腹腔注射vehicle或DEX,并使用画刷轻触刺激的方式测定小鼠三叉神经分布区域(V2,V3区)的DA疼痛评分,免疫荧光染色检测三叉神经病理性疼痛后内侧前额叶皮层(mPFC)神经元激活情况,以及使用DEX后的镇痛效果。【结果】与Sham组相比,CCI-ION组小鼠在术后3 d或7 d可引起同侧和对侧V2、V3区域的DA反应(P=0.0048;P<0.0001),同时双侧大脑mPFC区域c-Fos(神经元兴奋性标记物)阳性神经元数量均显著上升(P=0.0441;P=0.0444)。与CCI-ION+vehicle组比较,15µg/kg与30µg/kg的DEX可缓解三叉神经病理性疼痛引起的双侧原发性和继发性反应(P<0.0001),降低双侧mPFC脑区神经元的兴奋性(P=0.0125;P=0.0488),两个浓度的DEX镇痛效果并无明显差异(P>0.05)。【结论】DEX可有效缓解CCI-ION后画刷轻触刺激诱导的双侧原发性和继发性DA反应,其作用可能是通过降低双侧mPFC脑区神经元的活性调控的。【Objective】To investigate the analgesic effect and mechanism of dexmedetomidine(DEX)on dynamic al-lodynia(DA)in mice with trigeminal neuropathic pain.【Methods】We established the model of trigeminal neuropathic pain in male mice by a chronic constriction injury(CCI)of the infraorbital branch of the trigeminal nerve(ION).Mice were randomly separated into the following groups:Sham,CCI-ION,CCI-ION+vehicle,CCI-ION+DEX,Sham+DEX(each group contained four to six mice).For the measurement of DA,the ipsilateral and contralateral skin of the whisker pad within the infraorbital territory(V2)or the lower jaw within the mandibular nerve territory(V3)were stimulated by light-moving brush strokes.We used immunofluorescence staining to evaluate the possible mechanisms.【Results】Com-pare with the sham group,light-moving brush strokes induced obvious DA in ipsilateral and contralateral skin of V2 terri-tory and V3 territory at 3 d or 7 d after CCI-ION surgery(P=0.0048;P<0.0001),and the number of c-Fos(a marker for neuronal excitability)positive cells in bilateral mPFC increased significantly(P=0.0441,P=0.0444).In addition,15µg/kg and 30µg/kg DEX separately alleviated bilateral primary and secondary DA induced by light-moving mechanical facial stimuli in mice with trigeminal neuropathic pain(P<0.0001),and decreased the excitability of neurons in bilat-eral mPFC(P=0.0125,P=0.0488).Furthermore,there was no significant difference in analgesic effect between the two concentrations of DEX(P>0.05).【Conclusions】DEX is a useful therapeutic approach for attenuating DA in trigeminal neuropathic pain disorders.This effect is associated with the inhibition of hyperexcitability of neurons in mPFC induced by light-moving mechanical facial stimuli after trigeminal neuropathic pain.

关 键 词：右美托咪定 前额叶皮层 C-FOS 神经病理性疼痛 

分 类 号：R338[医药卫生—人体生理学]