Glutamate is the main excitatory neurotransmitter in the nervous system and plays a critical role in nociceptive processing and pain modulation. G-protein coupled metabotropic glutamate receptors (mGluRs) are widely expressed in the central and peripheral nervous system, and they mediate neuronal excitability and synaptic transmission. Eight different mGluR subtypes have been identified so far, and are classified into Groups I-III. Group II mGluR2 and mGluR3 couple negatively to adenylyl cyclase through Gi/Go proteins, are mainly expressed presynaptically, and typically inhibit the release of neurotransmitters, including glutamate and GABA. Group II mGluRs have consistently been linked to pain modulation; they are expressed in peripheral, spinal and supraspinal elements of pain-related neural processing. Pharmacological studies have shown anti-nociceptive/analgesic effects of group II mGluR agonists in preclinical models of acute and chronic pain, although much less is known about mechanisms and sites of action for mGluR2 and mGluR3 compared to other mGluRs. The availability of orthosteric and new selective allosteric modulators acting on mGluR2 and mGluR3 has provided valuable tools for elucidating (subtype) specific contributions of these receptors to the pathophysiological mechanisms of pain and other disorders and their potential as therapeutic targets. This review focuses on the important role of group II mGluRs in the neurobiology of pain mechanisms and behavioral modulation, and discusses evidence for their therapeutic potential in pain.

中文翻译：

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第二组代谢型谷氨酸受体：在疼痛机制和疼痛调节中的作用。


谷氨酸是神经系统中主要的兴奋性神经递质，在伤害性处理和疼痛调节中发挥着关键作用。 G 蛋白偶联代谢型谷氨酸受体 (mGluR) 广泛表达于中枢和周围神经系统，介导神经元兴奋性和突触传递。迄今为止，已鉴定出八种不同的 mGluR 亚型，并分为 I-III 组。 II 组 mGluR2 和 mGluR3 通过 Gi/Go 蛋白与腺苷酸环化酶负偶联，主要在突触前表达，通常抑制神经递质（包括谷氨酸和 GABA）的释放。 II 组 mGluR 一直与疼痛调节相关；它们在与疼痛相关的神经处理的外周、脊髓和脊髓上元件中表达。药理学研究表明，II 组 mGluR 激动剂在急性和慢性疼痛的临床前模型中具有抗伤害/镇痛作用，尽管与其他 mGluR 相比，我们对 mGluR2 和 mGluR3 的机制和作用位点知之甚少。作用于 mGluR2 和 mGluR3 的正构调节剂和新型选择性变构调节剂的出现，为阐明这些受体（亚型）对疼痛和其他疾病的病理生理机制的特定贡献及其作为治疗靶点的潜力提供了有价值的工具。本综述重点关注 II 类 mGluR 在疼痛机制和行为调节的神经生物学中的重要作用，并讨论了其治疗疼痛潜力的证据。