Department of Pharmacology and Neuroscience, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
Cells. 2022 Aug 21;11(16):2608. doi: 10.3390/cells11162608.
Metabotropic glutamate receptors (mGluR or mGlu) are G-protein coupled receptors activated by the binding of glutamate, the main classical neurotransmitter of the nervous system. Eight different mGluR subtypes (mGluR1-8) have been cloned and are classified in three groups based on their molecular, pharmacological and signaling properties. mGluRs mediate several physiological functions such as neuronal excitability and synaptic plasticity, but they have also been implicated in numerous pathological conditions including pain. The availability of new and more selective allosteric modulators together with the canonical orthosteric ligands and transgenic technologies has led to significant advances in our knowledge about the role of the specific mGluR subtypes in the pathophysiological mechanisms of various diseases. Although development of successful compounds acting on mGluRs for clinical use has been scarce, the subtype-specific-pharmacological manipulation might be a compelling approach for the treatment of several disorders in humans, including pain; this review aims to summarize and update on preclinical evidence for the roles of different mGluRs in the pain system and discusses knowledge gaps regarding mGluR-related sex differences and neuroimmune signaling in pain.
代谢型谷氨酸受体（mGluR 或 mGlu）是一种 G 蛋白偶联受体，通过与谷氨酸结合而被激活，谷氨酸是神经系统的主要经典神经递质。已经克隆出 8 种不同的 mGluR 亚型（mGluR1-8），并根据其分子、药理学和信号转导特性分为三组。mGluRs 介导多种生理功能，如神经元兴奋性和突触可塑性，但它们也与许多病理状况有关，包括疼痛。新型和更具选择性的变构调节剂的出现，加上经典的正位配体和转基因技术，使我们对特定 mGluR 亚型在各种疾病的病理生理机制中的作用有了更深入的了解。尽管针对 mGluR 的临床应用的成功化合物的开发很少，但对特定亚型的药理学干预可能是治疗人类多种疾病（包括疼痛）的一种有吸引力的方法。本文旨在总结和更新不同 mGluR 在疼痛系统中的作用的临床前证据，并讨论与 mGluR 相关的性别差异和神经免疫信号在疼痛中的知识空白。
