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

QI Zhi-hui; LI Jing; WANG Zhong-xing; HU Rong

doi:10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2022.0605

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

Basic Research | 更新时间：2024-02-19

- Dexmedetomidine Attenuates Dynamic Allodynia in a Mouse Model of Trigeminal Neuropathic Pain
- Journal of Sun Yat-sen University(Medical Sciences) Vol. 43, Issue 6, Pages: 898-904(2022)
- 作者机构：
  
  中山大学附属第一医院麻醉科，广东广州 510080
- 作者简介：
  
  HU Rong；E-mail：hurong27@mail.sysu.edu.cn
- 基金信息：
- DOI：10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2022.0605
  CLC： R338
- Received：11 June 2022，
  
  Published：20 November 2022
- 稿件说明：
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戚智慧,李静,王钟兴等.右美托咪定缓解三叉神经痛小鼠动态痛觉超敏反应[J].中山大学学报（医学科学版）,2022,43(06):898-904.

QI Zhi-hui,LI Jing,WANG Zhong-xing,et al.Dexmedetomidine Attenuates Dynamic Allodynia in a Mouse Model of Trigeminal Neuropathic Pain[J].Journal of Sun Yat-sen University(Medical Sciences),2022,43(06):898-904.
戚智慧,李静,王钟兴等.右美托咪定缓解三叉神经痛小鼠动态痛觉超敏反应[J].中山大学学报（医学科学版）,2022,43(06):898-904. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2022.0605.

QI Zhi-hui,LI Jing,WANG Zhong-xing,et al.Dexmedetomidine Attenuates Dynamic Allodynia in a Mouse Model of Trigeminal Neuropathic Pain[J].Journal of Sun Yat-sen University(Medical Sciences),2022,43(06):898-904. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2022.0605.

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（

=0.004 8；

＜0.000 1），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（

=0.044 1；

=0.044 4）。与CCI-ION+vehicle组比较，15 μg/kg与30 μg/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（

＜0.000 1），降低双侧mPFC脑区神经元的兴奋性（

=0.012 5；

=0.048 8），两个浓度的DEX镇痛效果并无明显差异（

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。

Abstract

Objective

To investigate the analgesic effect and mechanism of dexmedetomidine （DEX） on dynamic allodynia （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

Compare with the sham group， light-moving brush strokes induced obvious DA in ipsilateral and contralateral skin of V2 territory and V3 territory at 3 d or 7 d after CCI-ION surgery （

=0.004 8；

0.000 1）， and the number of c-Fos

（a marker for neuronal excitability） positive cells in bilateral mPFC increased significantly （

=0.044 1 ，

=0.044 4）. In addition， 15 μg/kg and 30 μg/kg DEX separately alleviated bilateral primary and secondary DA induced by light-moving mechanical facial stimuli in mice with trigeminal neuropathic pain （

0.000 1）， and decreased the excitability of neurons in bilateral mPFC （

0.012 5，

=0.048 8）. Furthermore， there was no significant difference in analgesic effect between the two concentrations of DEX （

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

Keywords

references

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Related Institution

Department of Physiology, Sun Yat-sen University School of Medicine

Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University

Department of Anesthesiology， Dongguan Tungwah Hospital

Department of Anesthesiology and Pain Clinic， The First Affiliated Hospital of Sun Yat-sen University

Department of Physiology， Zhongshan School of Medical， Sun Yat-sen University //Center for Pain Research， Sun Yat-sen University

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