Translatome profiling of spinal cord astrocytes reveals distinct gene signatures associated with acute and chronic pain.

Astrocytes coordinate neuronal signaling in physiological conditions but can also drive neuroinflammation in pathophysiologic conditions, such as chronic pain. How and when astrocyte molecular pathways change in response to pain-inducing peripheral injury is key to understanding the acute-to-chronic pain transition. Here, we utilize translating ribosome affinity purification technology in a mouse model of complex regional pain syndrome to uncover the functional molecular signature of spinal astrocytes early and late post-injury. We find that astrocytes exhibit a temporally distinct translatome with most significant gene expression changes occurring acutely after injury. We further identify astrocyte lipid metabolism as altered after injury and demonstrate that lipid droplets (marked by PLIN2) accumulate in the spinal dorsal horn in the chronic post-injury phase. Overall, this work provides an astrocyte-specific translatome resource for understanding spinal astrocyte contributions to pain and highlights spinal cord lipid metabolism as a pathway of interest in pain pathophysiology.