性别相关的口腔面疼痛机制的研究还远远不够。对于两性存在的组织特异性三叉神经感觉神经元在疾病状态下的全面调控，仍存在重大的知识空白。我们使用流式细胞术与逆行标记的感觉神经元进行RNA测序，以确定在雌雄小鼠的原始状态和携带舌部肿瘤的条件下，转录组谱面发生的变化。我们的数据揭示了以下有趣的发现：(1) 与雄性三叉神经节(TG)相比，流式细胞术可从雌性TG获得更多的神经元；(2) 在原始状态下，舌部感觉神经元中的雌性表达免疫细胞标记物如Csf1R、C1qa等，这些标记物在雄性中并未表达。这一结果经免疫组化法验证；(3) 相应地，免疫细胞标记物如Csf1只在雌性TG神经元中敏感化TRPV1反应；(4) 在肿瘤生长过程中，男性神经元的调节比女性神经元更加紧密，两性间重叠的差异表达基因(DEGs)很少；(5) 男性DEGs含有更多的转录因子，而女性DEGs含有更多的酶、细胞因子和趋化因子。综上所述，这是第一项研究性别以及舌部肿瘤对舌部感觉神经元全基因表达、通路和分子功能的影响的研究。© 2023. Springer Nature Limited.

Mechanisms of sex-dependent orofacial pain are widely understudied. A significant gap in knowledge exists about comprehensive regulation of tissue-specific trigeminal sensory neurons in diseased state of both sexes. Using RNA sequencing of FACS sorted retro-labeled sensory neurons innervating tongue tissue, we determined changes in transcriptomic profiles in males and female mice under naïve as well as tongue-tumor bearing conditions Our data revealed the following interesting findings: (1) FACS sorting obtained higher number of neurons from female trigeminal ganglia (TG) compared to males; (2) Naïve female neurons innervating the tongue expressed immune cell markers such as Csf1R, C1qa and others, that weren't expressed in males. This was validated by Immunohistochemistry. (3) Accordingly, immune cell markers such as Csf1 exclusively sensitized TRPV1 responses in female TG neurons. (4) Male neurons were more tightly regulated than female neurons upon tumor growth and very few differentially expressed genes (DEGs) overlapped between the sexes, (5) Male DEGs contained higher number of transcription factors whereas female DEGs contained higher number of enzymes, cytokines and chemokines. Collectively, this is the first study to characterize the effect of sex as well as of tongue-tumor on global gene expression, pathways and molecular function of tongue-innervating sensory neurons.© 2023. Springer Nature Limited.