TRIGEMINAL GANGLION GENE EXPRESSION IS MODULATED BY VITAMIN D<SUB>3</SUB> IN A MODEL OF OROFACIAL INFLAMMATION

The active form of cholecalciferol (vitamin D3; VD) exerts non-classical actions beyond calcium homeostasis, including roles in immune modulation and nociceptive processing. These effects are mediated by hormone-bound VD receptor (VDR) signaling; however, its contribution to gene regulation in the peripheral sensory system remains poorly defined. This study examined the impact of VD on pro-inflammatory, neurotrophic, antioxidant, and antinociceptive gene expression in the trigeminal ganglion (TG) in a rat model of orofacial inflammation.
Adult female Wistar rats received a single oral megadose of VD prior to induction of orofacial inflammation by subcutaneous injection of complete Freund’s adjuvant (CFA) into the vibrissal pad. TGs were collected three days later for RT-qPCR analysis.
CFA induced local edema and mechanical hyperalgesia and significantly increased mRNA expression of key mediators of peripheral sensitization, including TNF-α, NGF, BDNF, and CGRP. VD treatment attenuated CFA-induced TNF-α and CGRP expression while enhancing NGF and BDNF transcription. VD also upregulated the antioxidant enzyme HO-1. Although CFA increased expression of both the nociceptive TRPA1 channel and the antinociceptive oxytocin receptor (OXYR), VD selectively enhanced OXYR expression without altering TRPA1 levels.
These findings indicate that VD modulates inflammatory and nociceptive signaling in the trigeminal system by suppressing pro-inflammatory mediators while enhancing antioxidant and antinociceptive pathways, supporting a role for VDR signaling in peripheral sensory plasticity.
PB. Kemenesi-Gedei was supported by the Hungarian Ministry of Culture and Innovation, National Research, Development and Innovation Fund, EKÖP-KDP-2024.
K. Csabafi was supported by SZAOK-KKA-SZGYA:2024.02.01-2026.01.31.
This work was supported by the 2020-1.1.2-PIACI-KFI-2020-00131 grant.