There is a lack of objective indicators to evaluate the treatment effect of burning mouth syndrome, a neuropathic pain of unknown causes. Therefore, this study aimed to evaluate potential salivary biomarkers by analyzing saliva before and after clonazepam treatment in patients with burning mouth syndrome. Saliva was collected from 23 patients with burning mouth syndrome before and 4 weeks after the topical administration of clonazepam. Patients were classified as responders (pain relief of 50% or more, n = 10) or non-responders (n = 13) based on pain relief after treatment. Clinical examination data of responders and non-responders were compared using Mann-Whitney U test and Fisher's exact test. Changes in the level of salivary biomarkers (salivary alpha-amylase, cortisol, calmodulin, alpha-enolase and interleukin-18) were evaluated before and after treatment using Wilcoxon signed-rank sum test, and their association with treatment response was examined using Fisher's exact test. The salivary biomarker levels showed no significant differences between the responders and non-responders. However, the change in salivary alpha-amylase activity after treatment revealed a significant difference between the two groups (p = 0.039). Although not all patients showed the same pattern, there was a difference in the alteration of salivary alpha-amylase activity before and after treatment between responders and non-responders. Further study is required to clarify whether there is a causal relationship between salivary alpha-amylase activity and treatment response. However, considering that salivary alpha-amylase activity is related to orofacial pain and psychological stress, this suggests the potential use of salivary alpha-amylase as a biomarker for burning mouth syndrome.
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