Development of core outcome sets for clinical trials in temporomandibular disorders: A study protocol.

BACKGROUND: Temporomandibular Disorder (TMD) is a generic term applied to describe musculoskeletal disorders that affect the temporomandibular joint (TMJ), the masticatory muscles and the related structures. TMD comprises two groups of disorders, namely intra-articular TMD and masticatory muscle disorders. There is still difficulty in establishing the effectiveness of different therapeutic modalities for TMD with robust evidence, despite the large volume of publications in the area. The lack of outcomes standardization may represent a limiting factor in the search for scientific evidence. OBJECTIVE: This study aims to develop a core outcome sets (COS) for clinical trials in intra-articular TMD and masticatory muscle disorders. METHODS: The protocol for determining the COS-TMD will consist of three phases: 1. Synthesis of TMD Management Intervention Outcomes. The identification of outcomes will be carried out through a systematic review, which will include randomized clinical trials that evaluated the effectiveness of interventions used in TMD management. 2. Through a two-round international Delphi survey, the list of outcomes will be scored by three panels of stakeholders. 3. A representative sample of key stakeholders will be invited to participate in a face-to-face meeting where they can discuss the results of the Delphi survey and determine the final core set. CONCLUSIONS: The implementation of this protocol will determine the COS-TMD, which will be made available for use in all TMD clinical studies. The use of COS when planning and reporting TMD clinical trials will reduce the risk of publication bias and enable proper comparison of results found by different studies.

Action of Hyaluronic Acid as a Damage-Associated Molecular Pattern Molecule and Its Function on the Treatment of Temporomandibular Disorders.

The temporomandibular joint is responsible for fundamental functions. However, mechanical overload or microtraumas can cause temporomandibular disorders (TMD). In addition to external factors, it is known that these conditions are involved in complex biological mechanisms, such as activation of the immune system, activation of the inflammatory process, and degradation of extracellular matrix (ECM) components. The ECM is a non-cellular three-dimensional macromolecular network; its most studied components is hyaluronic acid (HA). HA is naturally found in many tissues, and most of it has a high molecular weight. HA has attributed an essential role in the viscoelastic properties of the synovial fluid and other tissues. Additionally, it has been shown that HA molecules can contribute to other mechanisms in the processes of injury and healing. It has been speculated that the degradation product of high molecular weight HA in healthy tissues during injury, a low molecular weight HA, may act as damage-associated molecular patterns (DAMPs). DAMPs are multifunctional and structurally diverse molecules that play critical intracellular roles in the absence of injury or infection. However, after cellular damage or stress, these molecules promote the activation of the immune response. Fragments from the degradation of HA can also act as immune response activators. Low molecular weight HA would have the ability to act as a pro-inflammatory marker, promoting the activation and maturation of dendritic cells, the release of pro-inflammatory cytokines such as interleukin 1 beta (IL-1ß), and tumor necrosis factor α (TNF-α). It also increases the expression of chemokines and cell proliferation. Many of the pro-inflammatory effects of low molecular weight HA are attributed to its interactions with the activation of toll-like receptors (TLRs 2 and 4). In contrast, the high molecular weight HA found in healthy tissues would act as an anti-inflammatory, inhibiting cell growth and differentiation, decreasing the production of inflammatory cytokines, and reducing phagocytosis by macrophages. These anti-inflammatory effects are mainly attributed to the interaction of high-weight HA with the CD44 receptor. In this study, we review the action of the HA as a DAMP and its functions on pain control, more specifically in orofacial origin (e.g., TMD).

Changes in the vibration sensitivity and pressure pain thresholds in patients with burning mouth syndrome.

OBJECTIVE: To investigate the presence of changes in vibration detection and pressure pain threshold in patients with burning-mouth syndrome (BMS). DESIGN OF THE STUDY: Case-control study. The sample was composed of 30 volunteers, 15 with BMS and 15 in the control group. The pressure-pain threshold (PPT) and vibration-detection threshold (VDT) were examined. The clinical evaluation was complemented with the McGill Pain Questionnaire (MPQ), Douleur Neuropathique 4 (DN4) and Beck Depression and Anxiety Inventories (BDI and BAI, respectively). RESULTS: BMS subjects showed a statistically significant higher PPT in the tongue (p = 0.002), right (p = 0.001) and left (p = 0.004) face, and a significant reduction of the VDT in the tongue (p = 0.013) and right face (p = 0.030). Significant differences were also found when comparing the PPT and the VDT of distinct anatomical areas. However, a significant interaction (group × location) was only for the PPT. BMS subjects also showed significantly higher levels of depression (p = 0.01), as measured by the BDI, compared to controls; and a significant inverse correlation between the VDT in the left face and anxiety levels was detected. CONCLUSIONS: The study of somatosensory changes in BMS and its correlations with the clinical features as well as the levels of anxiety and depression expands current understanding of the neuropathic origin and the possible contribution of psychogenic factors related to this disease.