Neuropathic pain is more prevalent in women. However, females are under-represented in animal experiments, and the mechanisms of sex differences remain inadequately understood. We used the spared nerve injury (SNI) model in rats to characterize sex differences in pain behaviour, unbiased RNA-Seq and proteomics to study the mechanisms. Male and female rats were subjected to SNI- and sham-surgery. Mechanical and cold allodynia were assessed. Ipsilateral lumbar dorsal root ganglia (DRG) and spinal cord (SC) segments were collected for RNA-seq analysis with DESeq2 on Day 7. Cerebrospinal fluid (CSF) samples for proteomic analysis and DRGs and SCs for analysis of IB-4 and CGRP, and IBA1 and GFAP, respectively, were collected on Day 21. Females developed stronger mechanical allodynia. There were no differences between the sexes in CGRP and IB-4 in the DRG or glial cell markers in the SC. No CSF protein showed change following SNI. DRG and SC showed abundant changes in gene expression. Sexually dimorphic responses were found in genes related to T-cells (cd28, ctla4, cd274, cd4, prf1), other immunological responses (dpp4, c5a, cxcr2 and il1b), neuronal transmission (hrh3, thbs4, chrna4 and pdyn), plasticity (atf3, c1qc and reg3b), and others (bhlhe22, mcpt1l, trpv6). We observed significantly stronger mechanical allodynia in females and numerous sexually dimorphic changes in gene expression following SNI in rats. Several genes have previously been linked to NP, while some are novel. Our results suggest gene targets for further studies in the development of new, possibly sex-specific, therapies for NP.

神经性疼痛在女性中更为普遍。然而，女性在动物实验中的代表性不足，性别差异的机制仍然没有得到充分了解。我们使用大鼠的备用神经损伤 (SNI) 模型来表征疼痛行为的性别差异、无偏见的 RNA-Seq 和蛋白质组学来研究机制。雄性和雌性大鼠接受 SNI 和假手术。评估机械和冷异常性疼痛。在第 7 天，收集同侧腰背根神经节 (DRG) 和脊髓 (SC) 节段，用 DESeq2 进行 RNA-seq 分析。脑脊液 (CSF) 样本用于蛋白质组学分析，DRG 和 SCs 用于分析 IB-4 和 CGRP，和 IBA1 和 GFAP 分别在第 21 天收集。女性出现更强的机械异常性疼痛。DRG 中的 CGRP 和 IB-4 或 SC 中的神经胶质细胞标志物的性别之间没有差异。SNI 后没有 CSF 蛋白显示变化。DRG 和 SC 显示出大量的基因表达变化。在与 T 细胞相关的基因中发现了性二态反应（cd28、ctla4、cd274、cd4、prf1）、其他免疫反应（dpp4、c5a、cxcr2和il1b）、神经元传递（hrh3、thbs4、chrna4和pdyn）、可塑性（atf3、c1qc和reg3b）和其他（bhlhe22、mcpt1l、trpv6）。我们观察到雌性显着更强的机械异常性疼痛和大鼠 SNI 后基因表达的许多性别二态变化。几个基因以前与 NP 相关，而有些是新的。我们的研究结果为进一步研究开发新的、可能具有性别特异性的 NP 疗法提供了基因靶点。