Translatome analysis reveals distinct spinal cord astrocyte gene signatures in 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 pai..., Mice
Adult male and female mice, 10-14 weeks old at the start of the experiment,s were housed 2-5 per cage and maintained on a 12-hour light/dark cycle in a temperature-controlled environment with ad libitum access to food and water. Male mice weighed approximately 25 g at the start of the study, and female mice weighed approximately 20 g at the start of the study. Mice used in this study: wild type C57BL/6J (Jax stock #00664), Aldh1l1-CreERT2 (Jax stock #029655), and Rpl22-HA (Jax stock #029977). To specifically and conditionally express the hemagglutinin epitope on the Rpl22 ribosomal subunit in astrocytes, we crossed hemizygous Aldh1l1-CreERT2 with homozygous Rpl22-HA and then subsequently back-crossed to homozygous Rpl22-HA. Thus, experimental animals were homozygous for the Rpl22-HA allele and hemizygous for the CreERT2 knock-in allele. Genotypes were determined using RT-PCR with probes designed for each gene (Transnetyx, Cordova, TN).
Study Approval
All procedures were approved by..., # Data from: Translatome analysis reveals distinct spinal cord astrocyte gene signatures in acute and chronic pain

Dataset DOI: [10.5061/dryad.jsxksn0qv](https://doi.org/10.5061/dryad.jsxksn0qv)

## Description of the data and file structure

This dataset includes individual data points generated from multiple independent experiments in Siliezar-Doyle et al. 2026 (accepted in principle). These include mouse behavioral assays, quantification of immunohistochemistry, and bulk RNA sequencing analysis using Weighted Gene Correlation Network Analysis (WGCNA) and differential gene expression analysis (DESEQ2). Data were collected over the period of 2020-2025.

### Files and variables

#### File: Dryad_WGCNA_All_significant_modules.xlsx

**Description:** Excel file containing gene lists that resulted from WGCNA analysis. These significant modules represent gene networks correlated to time point conditions (3-, 5-, and 7-weeks post-injury) with the baseline samples as the comparison cohort.

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