Abstract
Mechanisms of sex-dependent orofacial pain are widely understudied. A significant gap in knowledge exists about the comprehensive regulation of tissue-specific trigeminal sensory neurons in diseased states of both sexes. Using RNA sequencing of FACS-sorted retro-labeled sensory neurons innervating tongue tissue, we determined changes in transcriptomic profiles in male and female mice under naïve as well as tongue-tumor-bearing conditions Our data revealed the following interesting findings: (1) FACS sorting obtained a 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 wasn’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 a higher number of transcription factors whereas female DEGs contained a higher number of enzymes, cytokines, and chemokines. Collectively, this is the first study to characterize the effect of sex as well as of tongue tumors on global gene expression, pathways, and molecular function of tongue-innervating sensory neurons.