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首页> 外文期刊>The European Journal of Neuroscience >Supraspinal metabotropic glutamate receptors: A target for pain relief and beyond
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Supraspinal metabotropic glutamate receptors: A target for pain relief and beyond

机译：Suspaspinal代谢型谷氨酸受体：缓解疼痛和超越目标

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Glutamate is the main excitatory neurotransmitter in the central nervous system, controlling the majority of synapses. Apart from neurodegenerative diseases, growing evidence suggests that glutamate is involved in psychiatric and neurological disorders, including pain. Glutamate signaling is mediated via ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs). So far, drugs acting via modulation of glutamatergic system are few in number, and all are associated with iGluRs and important side effects. The glutamatergic system may be finely modulated by mGluRs. Signaling via these receptors is slower and longer-lasting, and permits fine-tuning of glutamate transmission. There have been eight mGluRs cloned to date (mGluR1-mGluR8), and these are further divided into three groups on the basis of sequence homology, pharmacological profile, and second messenger signaling. The pattern of expression of mGluRs along the pain neuraxis makes them suitable substrates for the design of novel analgesics. This review will focus on the supraspinal mGluRs, whose pharmacological manipulation generates a variety of effects, which depend on the synaptic location, the cell type on which they are located, and the expression in particular pain modulation areas, such as the periaqueductal gray, which plays a major role in the descending modulation of pain, and the central nucleus of the amygdala, which is an important center for the processing of emotional information associated with pain. A particular emphasis will also be given to the novel selective mGluR subtype ligands, as well as positive and negative allosteric modulators, which have permitted discrimination of the individual roles of the different mGluR subtypes, and subtle modulation of central nervous system functioning and related disorders.
机译：谷氨酸是中枢神经系统中主要的兴奋性神经递质，控制着大多数的突触。除神经退行性疾病外，越来越多的证据表明谷氨酸与精神和神经疾病有关，包括疼痛。谷氨酸信号传导是通过离子型谷氨酸受体（iGluRs）和代谢型谷氨酸受体（mGluRs）介导的。迄今为止，通过调节谷氨酸能系统起作用的药物数量很少，并且都与iGluR和重要的副作用有关。谷氨酸能系统可以通过mGluR精细调节。通过这些受体发出的信号较慢且持续时间较长，可以对谷氨酸的传递进行微调。迄今为止已克隆了八种mGluR（mGluR1-mGluR8），根据序列同源性，药理学特征和第二信使信号转导将它们进一步分为三类。沿着疼痛神经的mGluRs表达模式使其成为设计新型镇痛药的合适底物。这篇综述将侧重于脊髓上mGluRs，其药理学操纵会产生多种作用，这取决于突触的位置，它们所位于的细胞类型以及特定的疼痛调节区域（如导水管周围的灰色区域）中的表达。在疼痛和杏仁核的中央核的递减调节中起主要作用，杏仁核是处理与疼痛有关的情绪信息的重要中心。还将特别强调新型的选择性mGluR亚型配体以及正和负变构调节剂，它们可以区分不同mGluR亚型的个体作用，以及对中枢神经系统功能和相关疾病的微妙调节。

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