Chronic pain is a frequent, distressing and poorly understood health problem. Plasticity of synaptic transmission in the nociceptive pathways after inflammation or injury is assumed to be an important cellular basis for chronic, pathological pain. Glutamate serves as the main excitatory neurotransmitter at key synapses in the somatosensory nociceptive pathways, in which it acts on both ionotropic and metabotropic glutamate receptors. Although conventionally postsynaptic, compelling anatomical and physiological evidence demonstrates the presence of presynaptic glutamate receptors in the nociceptive pathways. Presynaptic glutamate receptors play crucial roles in nociceptive synaptic transmission and plasticity. They modulate presynaptic neurotransmitter release and synaptic plasticity, which in turn regulates pain sensitization. In this review, we summarize the latest understanding of the expression of presynaptic glutamate receptors in the nociceptive pathways, and how they contribute to nociceptive information processing and pain hypersensitivity associated with inflammation / injury. We uncover the cellular and molecular mechanisms of presynaptic glutamate receptors in shaping synaptic transmission and plasticity to mediate pain chronicity, which may provide therapeutic approaches for treatment of chronic pain.

慢性疼痛是一种常见、令人痛苦且人们知之甚少的健康问题。炎症或损伤后伤害感受通路中突触传递的可塑性被认为是慢性病理性疼痛的重要细胞基础。谷氨酸是体感伤害性通路中关键突触的主要兴奋性神经递质，作用于离子型和代谢型谷氨酸受体。尽管传统上是突触后，但令人信服的解剖学和生理学证据表明，伤害性通路中存在突触前谷氨酸受体。突触前谷氨酸受体在伤害性突触传递和可塑性中起着至关重要的作用。它们调节突触前神经递质的释放和突触可塑性，进而调节疼痛敏化。在这篇综述中，我们总结了对伤害性通路中突触前谷氨酸受体表达的最新理解，以及它们如何促进与炎症/损伤相关的伤害性信息处理和疼痛超敏反应。我们揭示了突触前谷氨酸受体塑造突触传递和可塑性以介导慢性疼痛的细胞和分子机制，这可能为治疗慢性疼痛提供治疗方法。