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代谢型谷氨酸受体7(mGluR 7)能否成为镇痛的新靶点?

Can Metabotropic Glutamate Receptor 7 (mGluR 7) be a Novel Target for Analgesia?

作者信息

G Shivaprakash, Suvarna Punya, Hadigal Sanjay, Kamath Priyanka, Prabhu Natesh, Shenoy K Ashok, Lc Pallavi

机构信息

Associate Professor, Department of Pharmacology, Kasturba Medical College, Manipal University , Manipal, Karnataka, India .

Undergraduate Medical Student, Department of Pharmacology, Kasturba Medical College, Manipal University , Mangalore, Karnataka, India .

出版信息

J Clin Diagn Res. 2014 Sep;8(9):HC16-8. doi: 10.7860/JCDR/2014/10377.4884. Epub 2014 Sep 20.

Abstract

INTRODUCTION

The present study was carried out to study the role of metabotropic glutamate receptor 7 (mGluR7) using its agonist, N,N'-bis(diphenylmethyl)-1,-ethanediamine (AMN082) for nociceptive stimuli, in animal models. By conducting this research, we aim to introduce a novel target for acute pain management.

OBJECTIVE

To study the role of metabotropic glutamate receptor 7 (mGluR7), in analgesia, using mGluR7 agonist AMN082 in animal models.

MATERIALS AND METHODS

Swiss albino mice of either sex, weighing 20-30gm were used for the study. The animals were divided into 3 groups with 6 mice in each group: Control or Normal group received 0.5% methylcellulose in normal saline; Standard group received the drug tramadol HCl at 40mg/kg; and test group received drug AMN 082 at 5mg/kg. All the drugs were administered by intraperitoneal route. Hot plate test and Tail flick test were done to evaluate the analgesic effect of the drug. Reaction time for the end points in both the models were noted before drug administration at 0 min and after drug administration at 15, 30,60,90 and 120 min. Statistical analysis was done using One-Way-ANOVA followed by Tukeys post hoc test. p-value was considered significant at ≤ 0.05.

RESULTS

The group that received AMN082 showed significantly lesser reaction time compared to normal and standard groups in both the analgesia models.

CONCLUSION

The mGluR 7 stimulation by an agonist AMN082, did not show analgesic effect but induced hyperalgesia in response to thermal nociceptive stimuli.

摘要

引言

本研究旨在利用代谢型谷氨酸受体7(mGluR7)的激动剂N,N'-双(二苯甲基)-1,2-乙二胺(AMN082),在动物模型中研究其对伤害性刺激的作用。通过开展这项研究,我们旨在引入一种用于急性疼痛管理的新靶点。

目的

在动物模型中,使用mGluR7激动剂AMN082研究代谢型谷氨酸受体7(mGluR7)在镇痛中的作用。

材料与方法

选用体重20-30克的瑞士白化小鼠,雌雄不限,用于本研究。将动物分为3组,每组6只小鼠:对照组或正常组接受生理盐水配制的0.5%甲基纤维素;标准组接受40mg/kg盐酸曲马多;试验组接受5mg/kg AMN 082。所有药物均通过腹腔注射给药。采用热板试验和甩尾试验评估药物的镇痛效果。在给药前0分钟以及给药后15、30、60、90和120分钟记录两种模型中终点的反应时间。采用单因素方差分析,随后进行Tukey事后检验进行统计分析。p值≤0.05被认为具有显著性。

结果

在两种镇痛模型中,接受AMN082的组与正常组和标准组相比,反应时间显著缩短。

结论

激动剂AMN082对mGluR 7的刺激并未显示出镇痛作用,反而在对热伤害性刺激的反应中诱发了痛觉过敏。

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The mGluR7 allosteric agonist AMN082 produces antidepressant-like effects by modulating glutamatergic signaling.
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