Department of Neurobiology, Fourth Military Medical University, Xi'an 710032, China.
Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Soochow University, Suzhou 215123, China.
Pharmacol Ther. 2023 Nov;251:108539. doi: 10.1016/j.pharmthera.2023.108539. Epub 2023 Sep 30.
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的、令人痛苦的且尚未被充分理解的健康问题。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。谷氨酸作为躯体感觉伤害感受通路上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。尽管传统上认为谷氨酸受体位于突触后，但有力的解剖学和生理学证据表明，伤害感受通路上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发挥着关键作用。它们调节突触前神经递质释放和突触可塑性，进而调节疼痛敏化。在这篇综述中，我们总结了伤害感受通路上突触前谷氨酸受体表达的最新认识，以及它们如何参与炎症/损伤相关的伤害性信息处理和痛觉过敏。我们揭示了突触前谷氨酸受体在调节疼痛慢性化的突触传递和可塑性中的细胞和分子机制，这可能为慢性疼痛的治疗提供了新的方法。
