Long-lasting pain stimuli can trigger maladaptive changes in the spinal cord, reminiscent of plasticity associated with memory formation. Metabolic coupling between astrocytes and neurons has been implicated in neuronal plasticity and memory formation in the central nervous system, but neither its involvement in pathological pain nor in spinal plasticity has been tested. Here we report a form of neuroglia signalling involving spinal astrocytic glycogen dynamics triggered by persistent noxious stimulation via upregulation of the Protein Targeting to Glycogen (PTG) in spinal astrocytes. PTG drove glycogen build-up in astrocytes, and blunting glycogen accumulation and turnover by Ptg gene deletion reduced pain-related behaviours and promoted faster recovery by shortening pain maintenance in mice. Furthermore, mechanistic analyses revealed that glycogen dynamics is a critically required process for maintenance of pain by facilitating neuronal plasticity in spinal lamina 1 neurons. In summary, our study describes a previously unappreciated mechanism of astrocyte–neuron metabolic communication through glycogen breakdown in the spinal cord that fuels spinal neuron hyperexcitability.

持久的疼痛刺激会引发脊髓的适应不良变化，让人想起与记忆形成相关的可塑性。星形胶质细胞和神经元之间的代谢耦合与中枢神经系统的神经元可塑性和记忆形成有关，但其与病理性疼痛和脊柱可塑性的关系尚未得到测试。在这里，我们报告了一种涉及脊髓星形胶质细胞糖原动力学的神经胶质信号传导形式，该信号传导是通过脊髓星形胶质细胞中糖原靶向蛋白（PTG）的上调而由持续的有害刺激触发的。PTG 促进星形胶质细胞中糖原的积累，通过Ptg基因缺失来抑制糖原的积累和周转，可以减少小鼠的疼痛相关行为，并通过缩短小鼠的疼痛维持时间来促进更快的恢复。此外，机制分析表明，糖原动力学是通过促进椎板 1 神经元的神经元可塑性来维持疼痛的关键必需过程。总之，我们的研究描述了一种以前未被认识到的星形胶质细胞-神经元代谢通讯机制，通过脊髓中的糖原分解来促进脊髓神经元过度兴奋。