Biological sex, gonadal hormones, and the epigenetic landscape collectively influence pain sensitivity, contributing to sex-based differences in pain perception. Females typically display heightened sensitivity to noxious stimuli, with estradiol's impact on hyperalgesia. Estradiol functions as a hormone released by peripheral steroidogenic organs or as neuroestradiol, locally synthesized in the nervous system by aromatase, which plays a crucial role in regulating neuroestradiol levels in pain circuits. This study investigates the role of neuroestradiol and its epigenetic involvement in the trigeminal ganglion (TG) of male and female adult mice. It explores the influence of gonadal sex, sex chromosome complement, and gonadal senescence on aromatase and epigenetic enzymes’ expression. The findings demonstrate aromatase immunoreactivity and gene expression in the TG of both genders, with higher levels in males. Using the four-core genotype transgenic model, which assesses the impact of ovarian hormones and sex chromosome complement, the study reveals that TG aromatase expression exclusively depends on sex hormones, displaying higher levels in animals with testes. Age and gonadal sex-dependent alterations in epigenetic markers are observed, along with multiple correlations with expression levels of aromatase, and various gonadal hormone receptors. Gonadal senescence increases aromatase expression in both sexes, particularly in females. This initial evidence of aromatase expression in a sensory peripheral ganglion, its sex-specific regulation by gonadal hormones, and potential epigenetic modulation provide new insights into the role of neuroestradiol in the local modulation of orofacial pain regulation at the pain pathway's entry point. Fundings: CAM-UAM (SI3-PJl-2021-00508), AEI and FEDER [PID2020-115019RBI00; PID2021-125039NB-I00J], CIBERFES, ISCIII.