Pain-related deactivation of medial prefrontal cortical neurons involves mGluR1 and GABAA receptors
Pain-related deactivation of medial prefrontal cortical neurons involves mGluR1 and GABAA receptors
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DOI：
10.1152/jn.00461.2011
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发表时间：
2011-11-01
影响因子：
2.5
通讯作者：
Neugebauer, Volker
中科院分区：
文献类型：
--
作者：
Ji, Guangchen;Neugebauer, Volker
张志强，张志强，张志强，等。脑皮层内侧神经元痛觉失活与mGluR1和GABA受体的关系。[J] .中国生物医学工程学报，2016,31(2):557 - 557。首次发表于2011年8月31日；doi: 10.1152 / jn.00461.2011。杏仁核疼痛相关的过度活跃导致内侧前额叶皮层失活和决策缺陷。疼痛相关的mPFC抑制机制尚不清楚。在这里，我们使用边缘前mPFC神经元的细胞外单单位记录来确定GABA(A)受体和代谢性谷氨酸受体（mGluR）亚型mGluR1和mGluR5在mPFC神经元疼痛相关活动变化中的作用。背景：关节炎诱导后，mPFC神经元的诱发活性降低。为了确定疼痛相关的变化，在关节内注射高岭土/卡拉胶诱导一个膝关节关节炎前后连续记录同一神经元。微透析立体定向给药GABA(a)受体拮抗剂{[R-(R*,S*)]-5-（6,8-二氢-8-氧-呋喃[3,4-e]-1,3-苯二酚-6-基）-5,6,7,8-四氢-6,6-二甲基-1,3-二氧唑[4,5-g]异喹啉碘化物（双库林）}进入mPFC可逆转疼痛相关抑制，而非原位注射到相邻的前扣带皮层对边缘前mPFC神经元没有或相反的影响。选择性mGluR1/5激动剂[(S)-3,5-二羟基苯基甘氨酸（DHPG）]在正常条件下通过gaba能机制抑制背景和激发活性，因为抑制作用被二环碱阻断。在关节炎疼痛状态下，DHPG单独使用或与二胡兰联合使用均无效果。与mGluR1参与疼痛相关的mPFC抑制一致，选择性mGluR1拮抗剂[(S)(+)- α -氨基-4-羧基-2-甲基苯乙酸]逆转了关节炎中mPFC神经元背景和诱发活性的疼痛相关下降，而选择性mGluR5拮抗剂[2-甲基-6-（苯乙基）盐酸吡啶]没有作用。mGluR拮抗剂在正常条件下无作用。我们解释了我们的数据，表明关节炎模型中mPFC神经元的疼痛相关抑制依赖于mglur1介导的GABA(A)受体的内源性激活。mGluR1/5的外源激活在正常情况下产生gaba能抑制。恢复mPFC的正常活动可能是改善与持续性疼痛相关的认知缺陷的治疗策略。
Ji G, Neugebauer V. Pain-related deactivation of medial prefrontal cortical neurons involves mGluR1 and GABA A receptors. J Neurophysiol 106: 2642-2652, 2011. First published August 31, 2011; doi: 10.1152/jn.00461.2011.-Pain-related hyperactivity in the amygdala leads to deactivation of the medial prefrontal cortex (mPFC) and decision-making deficits. The mechanisms of pain-related inhibition of the mPFC are not yet known. Here, we used extracellular single-unit recordings of prelimbic mPFC neurons to determine the role of GABA(A) receptors and metabotropic glutamate receptor (mGluR) subtypes, mGluR1 and mGluR5, in pain-related activity changes of mPFC neurons. Background and evoked activity of mPFC neurons decreased after arthritis induction. To determine pain-related changes, the same neuron was recorded continuously before and after induction of arthritis in one knee joint by intra-articular injection of kaolin/carrageenan. Stereotaxic administration of a GABA(A) receptor antagonist {[R-(R*,S*)]-5-(6,8-dihydro-8-oxo-furo[3,4-e]-1,3-benzodioxol-6-yl)-5,6,7,8-tetrahydro-6,6-dimethyl-1,3-dioxolo[4,5-g]isoquinolinium iodide (bicuculline)} into the mPFC by microdialysis reversed pain-related inhibition, whereas offsite injections into the adjacent anterior cingulate cortex had no or opposite effects on prelimbic mPFC neurons. A selective mGluR1/5 agonist [(S)-3,5-dihydroxyphenylglycine (DHPG)] inhibited background and evoked activity under normal conditions through a GABAergic mechanism, because the inhibitory effect was blocked with bicuculline. In the arthritis pain state, DHPG, alone or in the presence of bicuculline, had no effect. Consistent with the involvement of mGluR1 in pain-related inhibition of the mPFC, a selective mGluR1 antagonist [(S)( +)-alpha-amino-4-carboxy-2-methylbenzeneacetic acid] reversed the pain-related decrease of background and evoked activity of mPFC neurons in arthritis, whereas a selective mGluR5 antagonist [2-methyl-6-(phenylethynyl)pyridine hydrochloride] had no effect. The mGluR antagonists had no effect under normal conditions. We interpret our data to suggest that pain-related inhibition of mPFC neurons in the arthritis model depends on mGluR1-mediated endogenous activation of GABA(A) receptors. Exogenous activation of mGluR1/5 produces GABAergic inhibition under normal conditions. Restoring normal activity in the mPFC may be a therapeutic strategy to improve cognitive deficits associated with persistent pain.