Burning mouth syndrome (BMS) is defined as a chronic pain condition, characterized symptomatically by a generalized or localized burning sensation in the oral cavity. Various drugs have been used in attempting to treat BMS, but there is insufficient evidence to show the effect of any effective treatment. The aim of this review was to assess the effectiveness of therapies for BMS. Randomized controlled trials (RCTs) enrolling patients with a diagnosis of BMS were identified by searching Pubmed and Scoppus databases. The methodological quality of included studies was assessed on the basis of the method of allocation concealment, blindness of the study, loss of participants, size sample, and outcome concealment. A total of 12 relevant articles were analyzed. Therapies that used capsaicin, alpha-lipoic acid (ALA), and clonazepam were those that showed more reduction in symptoms of BMS. However, many studies of therapeutic interventions in BMS lack consistency in their results, because they use in their methodology, sample and a relatively short time of therapy and often do not provide a follow-up of patients treated. Thus, future studies are required to establish the treatment for patients suffering from this chronic and painful syndrome.

Hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) are proteins that stimulate the proliferation and migration of endothelial cells. These proteins have been described in many pathologic and inflammatory conditions, but their involvement in the development of periodontitis has not been thoroughly investigated. This study compared the immunohistochemical expression of these proteins, involved in angiogenesis and hypoxia, by immunostained inflammatory and endothelial cells in periodontal disease and healthy gingival tissues. Gingival tissue samples were divided as follows: 30 samples with chronic periodontitis, 30 with chronic gingivitis, and 30 of healthy gingiva. Results were analyzed statistically by the Kruskal-Wallis, Mann-Whitney and Spearman correlation tests (p=0.01). Inflammatory and endothelial cells were found to express these proteins. Periodontitis showed median percentage of HIF-1α-positive cells of 39.6%, 22.0% in cases of gingivitis and 0.9% in the healthy gingiva group (p=0.001). For VEGF, median percentage of immunopositive cells was 68.7% for periodontitis, 66.1% in cases for gingivitis, and 19.2% for healthy gingival specimens (p<0.001). Significant correlation between VEGF and HIF-1α was also observed in healthy gingiva (p<0.001).The increased expression of HIF-1α and VEGF in periodontitis, compared to gingivitis and healthy gingiva, suggests possible activation of the HIF-1α pathway in advanced periodontal disease. The correlation between HIF-1α and VEGF expression in healthy gingiva suggests a physiological function for these proteins in conditions of homeostasis. In periodontal disease, HIF-1α and VEGF expression may be regulated by other factors, in addition to hypoxia, such as bacterial endotoxins and inflammatory cytokines.

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