Antagonism of Cannabinoid Receptor 1 Attenuates the Anti-Inflammatory Effects of Electroacupuncture in a Rodent Model of Migraine
Antagonism of Cannabinoid Receptor 1 Attenuates the Anti-Inflammatory Effects of Electroacupuncture in a Rodent Model of Migraine
复制标题
DOI：
10.1136/acupmed-2016-011113
复制
发表时间：
2016-11
影响因子：
2.5
通讯作者：
Hui Zhang;Shengdong He;You-ping Hu;Hui-E Zheng
中科院分区：
文献类型：
--
作者：
Hui Zhang;Shengdong He;You-ping Hu;Hui-E Zheng
背景：电针治疗偏头痛的抗伤害性效应已在多项随机对照试验中得到证实。神经源性炎症在偏头痛发作中起着关键作用，针灸的抗炎作用与1型大麻素（CB 1）受体有关。目的探讨CB 1受体是否介导电针对偏头痛发作的抗炎作用。方法采用电刺激单侧三叉神经节（TGES）的方法建立偏头痛大鼠模型。在TGES前5天每天电针一次，同时腹腔注射CB 1受体拮抗剂SR 141716（TGES+EA+ SR 141716组）或不注射SR 141716（TGES+EA组）。另一组TGES大鼠（TGES+MA组）和非TGES假手术组（Sham+MA组）接受微针（MA）。在TGES开始时和5 min后，测定同侧颈静脉血中降钙素基因相关肽（CGRP）和前列腺素E2（PGE 2）的浓度。死后检测三叉神经节（TG）中白细胞介素（IL）-1β和环氧合酶（考克斯）2蛋白水平以及硬脑膜中血浆蛋白外渗（PPE）。结果TGES诱导血清CGRP和PGE 2水平升高（TGES+MA vs基础和vs Sham：均p<0.001），TG中IL-1β和COX 2蛋白表达增加，神经源性PPE水平升高（TGES+MA vs Sham+MA：均p<0.001）。EA减弱了TGES诱导的这些蛋白质水平的增加（TGES+EA vs TGES+MA：所有p<0.001）。CB 1受体拮抗剂逆转了EA的作用（TGES+EA+ SR 141716 vs TGES+EA：所有p<0.05）。结论CB 1受体介导了电针对偏头痛大鼠的抗炎作用。
Background The anti-nociceptive effects of electroacupuncture (EA) in migraine have been documented in multiple randomised controlled trials. Neurogenic inflammation plays a key role in migraine attacks, and the anti-inflammatory effects of acupuncture have been associated with the type 1 cannabinoid (CB1) receptor. Objective To investigate whether CB1 receptors mediate the anti-inflammatory effects of EA on migraine attacks. Methods A migraine model was produced in Sprague-Dawley rats by unilateral electrical stimulation of the trigeminal ganglion (TGES). Rats received EA daily on the 5 days preceding TGES with (TGES+EA+SR141716 group) or without (TGES+EA group) intraperitoneal injections of the CB1 receptor antagonist SR141716. Another group of TGES rats (TGES+MA group) and a non-TGES sham-operated group of rats (Sham+MA group) received minimal acupuncture (MA). Calcitonin gene-related peptide (CGRP) and prostaglandin E2 (PGE2) concentrations were determined in serum obtained from the ipsilateral jugular vein at initiation of TGES and 5 min after. Postmortem interleukin (IL)-1β and cyclooxygenase (COX)2 protein levels in the trigeminal ganglion (TG) and plasma protein extravasation (PPE) in the dura mater were assessed. Results TGES induced increases in serum CGRP and PGE2 levels (TGES+MA vs baseline and vs Sham: all p<0.001), as well as IL-1β and COX2 protein expression in the TG, and neurogenic PPE levels (TGES+MA vs Sham+MA: all p<0.001). EA attenuated TGES-induced increases in the levels of these proteins (TGES+EA vs TGES+MA: all p<0.001). CB1 receptor antagonism reversed the effects of EA (TGES+EA+SR141716 vs TGES+EA: all p<0.05). Conclusions CB1 receptors appear to mediate anti-inflammatory effects of EA in a rat model of migraine.