Oxytocin receptor (OXTR), a G protein-coupled receptor, has been demonstrated to play a significant role in analgesia after activation by its canonical agonist, oxytocin (OXT) in the dorsal root ganglion (DRG). However, the role of OXTR in the trigeminal nervous system on the orofacial neuropathic pain is still little known. In the present study, we aimed to investigate the regulation effect and mechanism of OXTR in the trigeminal ganglion (TG) and spinal trigeminal nucleus caudalis (SpVc) on orofacial ectopic pain induced by trigeminal nerve injury. Inferior alveolar nerve (IAN) was transected to establish trigeminal ectopic pain model. Von Frey filaments behavioral test demonstrated IAN transection (IANX) evoked mechanical hypersensitivity in the whisker pad since from day 1 to at least day 14 after surgery. In addition, administration of OXT (50 μM and 100 μM) into the TG attenuated the mechanical hypersensitivity induced by IANX, which was reversed by pre-treatment with L-368,899 (a selective antagonist of OXTR) into the TG. In addition, immunofluorescence (IF) showed the expression of OXTR in neurons in the TG and SpVc. Furthermore, western blot (WB) analysis indicated that the upregulated expression of OXTR, calcitonin gene-related peptide (CGRP), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the TG and SpVc after IANX was inhibited by the administration of OXT into the TG. And the inhibition effect of OXT on the expression of CGRP, IL-1β, and TNF-α was abolished by pre-application of L-368,899 into the TG.
Macrophages in trigeminal ganglion contribute to ectopic mechanical hypersensitivity following inferior alveolar nerve injury in rats
