Yang Jing, Xue Xiaoling, Yang Zhi, Hao Fei, Chen Bangtao
Department of Dermatology, Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, People's Republic of China.
Department of Pathogenic Biology, College of Basic Medical Sciences, Jinzhou Medical University, Jinzhou, 121001, People's Republic of China.
J Inflamm Res. 2025 Jun 17;18:7907-7919. doi: 10.2147/JIR.S525663. eCollection 2025.
To profile spinal medium- and long- chain fatty acids (ML-CFAs) and itch-related gene expressions (IRGEs) in dorsal root ganglion (DRG), and investigate the role of spinal palmitic acid (PA) in atopic dermatitis (AD), and its relationship with DRG and spinal extracellular signal-regulated kinase (ERK).
MC903 was applied topically to the nape of C57BL/6 mice to induce AD. Two doses of PA were administered intrathecally during MC903 treatment, and several antagonists were administered intrathecally one day before PA challenge. Transcriptome sequencing was performed on DRGs, and 36 ML-CFAs in the spinal cord were analyzed.
A global upregulation of IRGEs in DRGs and increases in major ML-CFAs including PA in the spinal cord were observed in adult AD model. MC903 resulted in less severe dermatitis with weaker IRGEs in DRGs and lower spinal ML-CFAs in senile than adult mice. In adult mice, intrathecal PA injection caused acute scratches, aggravated AD, and induced stronger IRGEs in DRGs. Intrathecal injection of transient receptor potential vanilloid-1 channel (TRPV1) antagonist capsazepine or Mas-related G protein-coupled receptor D (MRGPRD) antagonist d-Pro7-ANG-(1-7) remarkably halted PA/MC903-induced dermatitis and PA-induced scratching. Administration of histamine h4 receptor antagonist JNJ7777120 only moderately alleviated dermatitis, with no notable effect on scratches. Intrathecal pan-palmitoylation inhibitor 2-Bromopalmitate moderately alleviated MC903/PA-induced lesions and spinal ERK phosphorylation. Intrathecal lidocaine markedly suppressed both lesions and ERK phosphorylation, along with a global reduction in IRGEs in DRGs. Finally, PA-induced scratches were significantly improved by intrathecal lidocaine but not 2-Bromopalmitate.
MC903-induced AD develops more readily in adult than senile mice, with consistent changes in IRGEs in DRG and spinal ML-CFA levels, including PA. Spinal PA promotes AD involving spinal TRPV1 and MRGPRD signaling, and IRGEs increments in DRG. Intrathecal lidocaine suppresses AD aggravated by PA via inhibiting spinal ERK phosphorylation and reducing IRGEs in DRG.
分析背根神经节（DRG）中脊髓中长链脂肪酸（ML-CFAs）及瘙痒相关基因表达（IRGEs），探讨脊髓棕榈酸（PA）在特应性皮炎（AD）中的作用及其与DRG和脊髓细胞外信号调节激酶（ERK）的关系。
将MC903局部应用于C57BL/6小鼠颈部诱导AD。在MC903治疗期间鞘内注射两剂PA，并在PA攻击前一天鞘内注射几种拮抗剂。对DRG进行转录组测序，并分析脊髓中的36种ML-CFAs。
在成年AD模型中观察到DRG中IRGEs整体上调，脊髓中包括PA在内的主要ML-CFAs增加。与成年小鼠相比，MC903在老年小鼠中引起的皮炎较轻，DRG中的IRGEs较弱，脊髓ML-CFAs较低。在成年小鼠中，鞘内注射PA导致急性搔抓、加重AD，并在DRG中诱导更强的IRGEs。鞘内注射瞬时受体电位香草酸受体1通道（TRPV1）拮抗剂辣椒素或Mas相关G蛋白偶联受体D（MRGPRD）拮抗剂d-Pro7-ANG-(1-7)可显著阻止PA/MC903诱导的皮炎和PA诱导的搔抓。组胺h4受体拮抗剂JNJ7777120仅适度减轻皮炎，对搔抓无明显影响。鞘内泛棕榈酰化抑制剂2-溴棕榈酸适度减轻MC903/PA诱导的损伤和脊髓ERK磷酸化。鞘内利多卡因显著抑制损伤和ERK磷酸化，同时DRG中IRGEs整体减少。最后，鞘内利多卡因可显著改善PA诱导的搔抓，但2-溴棕榈酸无效。
MC903诱导的AD在成年小鼠中比老年小鼠更容易发生，DRG中的IRGEs和脊髓ML-CFA水平（包括PA）有一致变化。脊髓PA通过脊髓TRPV1和MRGPRD信号促进AD，并增加DRG中的IRGEs。鞘内利多卡因通过抑制脊髓ERK磷酸化和减少DRG中的IRGEs来抑制PA加重的AD。
