Abstract
Pain is one of the main reasons for patients with temporomandibular joint (TMJ) disorders seeking medical care. However, there is no effective treatment yet as its mechanism remains unclear. Herein, we found that the injection of monoiodoacetate (MIA) into mice TMJs can induce typical joint pain as early as 3 days, accompanied by an increased percentage of calcitonin gene-related peptide positive (CGRP+) neurons and isolectin B4 positive (IB4+) in the trigeminal ganglions (TGs). Our previous study has discovered that alpha-kinase 1 (ALPK1) may be involved in joint pain. Here, we detected the expression of ALPK1 in neurons of TGs in wild-type (WT) mice, and it was upregulated after intra-TMJ injection of MIA. Meanwhile, the increased percentage of neurons in TGs expressing ALPK1 and CGRP or ALPK1 and IB4 was also demonstrated by the immunofluorescent double staining. Furthermore, after the MIA injection, ALPK1-/- mice exhibited attenuated pain behavior, as well as a remarkably decreased percentage of IB4+ neurons and an unchanged percentage of CGRP+ neurons, as compared with WT mice. In vitro assay showed that the value of calcium intensity was weakened in Dil+ neurons from ALPK1-/- mice of TMJ pain induced by the MIA injection, in relation to those from WT mice, while it was significantly enhanced with the incubation of recombinant human ALPK1 (rhA). Taken together, these results suggest that ALPK1 promotes mice TMJ pain induced by MIA through upregulation of the sensitization of IB4+ neurons in TGs. This study will provide a new potential therapeutic target for the treatment of TMJ pain.