Department of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine, Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China.
School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, China.
Mol Pain. 2023 Jan-Dec;19:17448069221106167. doi: 10.1177/17448069221106167.
Chemotherapy-induced peripheral neuropathy (CIPN) is the most common side-effect of anti-cancer therapy. To date, there are no clinically effective analgesics that could prevent and treat CIPN. However, the exact pathogenesis of CIPN is still unclear. In the present study, we use the paclitaxel-induced peripheral neuropathy (PIPN) model, aiming to better understand the transcriptomic level of the Dorsal root ganglia (DRG) neurons in rats with PIPN. mRNA from each DRG sample was reverse transcribed to cDNA and sequenced using next-generation high throughput sequencing technology. Quantitative RT-PCR verification was used to confirm the identified Differentially expressed genes (DEGs) in the DRG of PIPN rats. RNAseq results have identified 384 DEGs (adjusted < 0.05; fold change ≥ 2) in the DRG of rats 14 days after paclitaxel injection in total, including 97 up-regulated genes, and 287 down-regulated genes. GO analysis revealed that these DEGs were majorly involved in neuropeptide activity, chemokine receptor activity, defense response, and inflammatory response. Kyoto Encyclopedia of Gene and Genomes analysis showed that neuroactive ligand-receptor interaction and cytokine-cytokine receptor interaction were involved in sensory neurons of rats with PIPN. Besides, comparison analysis identified that 11 DEGs in the PIPN model are shared with either inflammatory pain (Ces1d, Cfd, Retn, and Fam150b) or neuropathic pain (Atf3, Csrp3, Ecel1, Gal, Sprr1a, Tgm1, and Vip). Quantitative RT-PCR results also confirmed the validation of the RNAseq data. These results suggested that neuroactive ligand-receptor interaction and cytokine-cytokine receptor interaction are majorly involved in sensory neurons of rats with PIPN. Immune, inflammatory responses and neuron functional changes are the major pathogenesis of PIPN. Paclitaxel-induced peripheral neuropathy has shared characteristics with both inflammatory pain and neuropathic pain.
化疗引起的周围神经病（CIPN）是癌症治疗中最常见的副作用。迄今为止，尚无临床有效的镇痛药可预防和治疗 CIPN。然而，CIPN 的确切发病机制尚不清楚。在本研究中，我们使用紫杉醇诱导的周围神经病（PIPN）模型，旨在更好地了解紫杉醇诱导的周围神经病大鼠背根神经节（DRG）神经元的转录组水平。从每个 DRG 样本中提取的 mRNA 反转录为 cDNA，并使用下一代高通量测序技术进行测序。采用定量 RT-PCR 验证来确认 PIPN 大鼠 DRG 中鉴定的差异表达基因（DEG）。RNAseq 结果总共在紫杉醇注射后 14 天的大鼠 DRG 中鉴定出 384 个 DEG（调整后 < 0.05；倍数变化≥2），包括 97 个上调基因和 287 个下调基因。GO 分析显示，这些 DEG 主要参与神经肽活性、趋化因子受体活性、防御反应和炎症反应。京都基因与基因组百科全书分析显示，神经活性配体-受体相互作用和细胞因子-细胞因子受体相互作用参与了 PIPN 大鼠感觉神经元。此外，比较分析表明，PIPN 模型中的 11 个 DEG 与炎症性疼痛（Ces1d、Cfd、Retn 和 Fam150b）或神经性疼痛（Atf3、Csrp3、Ecel1、Gal、Sprr1a、Tgm1 和 Vip）共享。定量 RT-PCR 结果也证实了 RNAseq 数据的验证。这些结果表明，神经活性配体-受体相互作用和细胞因子-细胞因子受体相互作用主要参与了 PIPN 大鼠感觉神经元。免疫、炎症反应和神经元功能变化是 PIPN 的主要发病机制。紫杉醇诱导的周围神经病具有炎症性疼痛和神经性疼痛的共同特征。
