Lactate transport is an important means of communication between astrocytes and neurons and is implicated in a variety of neurobiological processes. However, the connection between astrocyte-neuron lactate transport and nociceptive modulation has not been well established. Here, we found that Complete Freund’s adjuvant (CFA)-induced inflammation pain leads to a significant increase in extracellular lactate levels in the anterior cingulate cortex (ACC). Inhibition of glycogenolysis and lactate release in the ACC disrupted the persistent, but not acute, inflammation pain induced by CFA, and this effect was reversed by exogenous L-lactate administration. Knocking down the expression of lactate transporters (MCT1, MCT4, or MCT2) also disrupted the long lasting inflammation pain induced by CFA. Moreover, glycogenolysis in the ACC is critical for the induction of molecular changes related to neuronal plasticity, including the induction of phospho- (p-) ERK, p-CREB, and Fos. Taken together, our findings indicate that astrocyte-neuron lactate transport in the ACC is critical for the occurrence of persistent inflammation pain, suggesting a novel mechanism underlying chronic pain.

乳酸转运是星形胶质细胞和神经元之间交流的重要手段，涉及多种神经生物学过程。然而，星形胶质细胞-神经元乳酸转运和伤害性调节之间的联系尚未得到很好的确立。在这里，我们发现完全弗氏佐剂 (CFA) 诱导的炎症疼痛导致前扣带皮层 (ACC) 中细胞外乳酸水平显着增加。ACC 中糖原分解和乳酸释放的抑制破坏了由 CFA 诱导的持续性但非急性的炎症疼痛，并且这种作用被外源性 L-乳酸给药逆转。降低乳酸转运蛋白（MCT1、MCT4 或 MCT2）的表达也破坏了由 CFA 引起的长期炎症疼痛。而且，ACC 中的糖原分解对于诱导与神经元可塑性相关的分子变化至关重要，包括磷酸化 (p-) ERK、p-CREB ​​和 Fos 的诱导。总之，我们的研究结果表明，ACC 中的星形胶质细胞-神经元乳酸转运对于持续性炎症疼痛的发生至关重要，这表明了慢性疼痛的新机制。