Inflammatory Orofacial Pain Activates Peptidergic Neurons and Upregulates the Oxytocin Receptor Expression in Trigeminal Ganglion

The majority of orofacial pain is caused by musculoskeletal and neuropathological diseases related to inflammatory processes that lead even to transcriptional alterations in the trigeminal ganglion (TG) neurons. The hypothalamic nonapeptide oxytocin has been reported to modulate nociception via binding and activating its receptor in primary sensory neurons. The purpose of this study was to analyze the gene expression of the oxytocin receptor (OTR), c-Fos, an indicator of neuronal activity, and alpha-calcitonin gene-related peptide (alpha CGRP), a characteristic neurotransmitter of the peptidergic trigeminal primary afferents in an animal model of inflammation-induced orofacial pain. Carrageenan was unilaterally injected into the vibrissal pads of male and female adult Wistar rats. RT-qPCR was performed to analyze the levels of mRNA expression in TGs 24 h after injection. The gene expression analysis revealed higher fold changes regarding the c-Fos (mean +/- S.E: female: 3.9 +/- 0.19; male: 3.55 +/- 0.18) and alpha CGRP (female: 2.84 +/- 0.13; male: 3.39 +/- 0.47) expression levels of mRNA, and a moderate rise in the expression of the OTR mRNA (female: 1.52 +/- 0.07; male: 1.49 +/- 0.07) was observed in comparison to both vehicle(saline)-treated and untreated controls. Our results furnish evidence for inflammation-induced activation of peptidergic neurons, and it is suggested that oxytocin modulates inflammation-induced nociception by enhancing their signaling capacity due to its elevated expression in the sensory ganglion cells, thus providing new therapies for orofacial pain relief that target the OTRs.