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Temporomandibular disorders (TMD) are a group of clinical problems affecting temporomandibular joint (TMJ), myofascial muscles and other related structures. Splint therapy is the most commonly used approach to treatment of TMD, but its effectiveness is remains unclear. We therefore conducted a meta-analysis to evaluate the effectiveness of splint therapy for TMD in adults. The electronic databases PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched for reports published up to March 31, 2016. Thirteen eligible studies involving 538 patients were identified. The results indicated that splint therapy increased maximal mouth opening (MMO) for patients with a MMO <45mm and reduced pain intensity measured using the visual analogue scale (VAS) for patients with TMD without specific description (TMDSD). Splint therapy also reduced the frequency of painful episodes for patients with TMJ clicking. No publication bias was observed, as determined with Egger's test for all outcomes. On the basis of this evidence, we recommend the use of splints for the treatment and control of TMD in adults.

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BackgroundMost people are initially infected with varicella zoster virus (VZV) at a young age and this infection results in chickenpox. VZV then becomes latent and reactivates later in life resulting in herpes zoster (HZ) or “shingles”. Often VZV infects neurons of the trigeminal ganglia to cause ocular problems, orofacial disease and occasionally a chronic pain condition termed post-herpetic neuralgia (PHN). To date, no model has been developed to study orofacial pain related to varicella zoster. Importantly, the incidence of zoster associated pain and PHN is known to be higher in women, although reasons for this sex difference remain unclear. Prior to this work, no animal model was available to study these sex-differences. Our goal was to develop an orofacial animal model for zoster associated pain which could be utilized to study the mechanisms contributing to this sex difference.MethodsTo develop this model VZV was injected into the whisker pad of rats resulting in IE62 protein expression in the trigeminal ganglia; IE62 is an immediate early gene in the VZV replication program.ResultsSimilar to PHN patients, rats showed retraction of neurites after VZV infection. Treatment of rats with gabapentin, an agent often used to combat PHN, ameliorated the pain response after whisker pad injection. Aversive behavior was significantly greater for up to 7 weeks in VZV injected rats over control inoculated rats. Sex differences were also seen such that ovariectomized and intact female rats given the lower dose of VZV showed a longer affective response than male rats. The phase of the estrous cycle also affected the aversive response suggesting a role for sex steroids in modulating VZV pain.ConclusionsThese results suggest that this rat model can be utilized to study the mechanisms of 1) orofacial zoster associated pain and 2) the sex differences underlying zoster associated pain.

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Purpose:The purpose of this study was to evaluate conventional acupuncture therapy in the management of clinical outcomes for temporomandibular disorders (TMD) in adults.Methods:The electronic databases PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Clinical Trails.gov were searched for reports published until March 31, 2016.Results:Nine eligible studies from 8 publications involving 231 patients were included in the meta-analysis. A comparison of the main outcome of visual analog scale (VAS) values of pain between the acupuncture group and control group showed a significant decrease (MD = −0.98, 95% CI [−1.62, −0.34], I2=54%, P = 0.003) in the VAS following acupuncture treatment. However, subgroup analysis according to the type of sham control group indicated that there were significant differences in the results when sham acupuncture was used as the control group (MD = −1.54, 95% CI [−2.63, −0.45], I2=58%, P = 0.006) as well as when sham laser treatment was used as the control group (MD = −1.29, 95% CI [−2.32, −0.27], I2 = 0%, P = 0.01). However, there was no significant difference when the splint treatment group was used as the control group (MD = −0.09, 95% CI [−0.69, 0.50], I2 = 0%, P = 0.76). Subgroup analyses of VAS for pain by the classification of diseases indicated that the myogenous TMD subgroup demonstrated a significant difference (MD = −1.49, 95% CI [−2.45, −0.53], I2 = 47%, P = 0.002), and TMD showed no statistically significant difference (MD = −0.42, 95% CI [−1.14, 0.30], I2 = 46%, P = 0.25). Subgroup analysis according to whether the subgroup penetrated the skin showed that nonpenetrating sham acupuncture as the control group showed a significant difference (MD = −1.56, 95% CI [−2.70, −0.41], I2 = 58%, P = 0.008) compared with the conventional acupuncture as the treatment modality, while penetrating sham acupuncture as the control group showed no significant difference (MD = −1.29, 95% CI [−3.40, 0.82], I2 = not applicable, P = 0.23). No publication bias was observed considering the symmetry of the funnel plots.Conclusions:Our results indicate that conventional acupuncture therapy is effective in reducing the degree of pain in patients with TMD, especially those with myofascial pain symptoms.

High mobility group 1 protein (HMGB1), a highly conserved nuclear DNA-binding protein and inflammatory mediator, has been recently found to be involved in angiogenesis. Our previous study has demonstrated the elevation of HMGB1 in the tissue of perforated disc of temporomandibular joint (TMJ). Here, we investigated a novel mediator of HMGB1 in regulating hypoxia-inducible factor-1a (HIF-1a) and vascular endothelial growth factor (VEGF) to mediate angiogenesis in perforated disc cells of TMJ. HMGB1 increased the expression of HIF-1a and VEGF in a dose-and time-dependent manner in these cells. Moreover, immunofluorescence assay exhibits that the HIF-1a were activated by HMGB1. In addition, HMGB1 activated extracellular signal-related kinase 1/2 (Erk1/2), Jun N-terminal kinase (JNK), but not P38 in these cells. Furthermore, both U0126 (ErK inhibitor) and SP600125 (JNK inhibitor) significantly suppressed the enhanced production of HIF-1a and VEGF induced by HMGB1. Tube formation of human umbilical vein endothelial cells (HUVECs) was significantly increased by exposure to conditioned medium derived from HMGB1-stimulated perforated disc cells, while attenuated with pre-treatment of inhibitors for VEGF, HIF-1a, Erk and JNK, individually. Therefore, abundance of HMGB1 mediates activation of HIF-1a in disc cells via Erk and JNK pathway and then, initiates VEGF secretion, thereby leading to disc angiogenesis and accelerating degenerative change of the perforated disc.