Activation of the kynurenine pathway in possible bruxism: associations with cortisol, TNF-α, and possible bruxism subtypes.

Objective: Bruxism (BR) is a repetitive activity of the masticatory muscles influenced by stress-related and neurophysiological mechanisms. Psychological stress activates the hypothalamic-pituitary-adrenal (HPA) axis, leading to cortisol release and modulation of immune responses and tryptophan (Trp) metabolism via the kynurenine (KYN) pathway. The KYN pathway is activated in various systemic and physiological disorders. However, whether KYN pathway activation occurs in BR remains unknown. Investigating KYN pathway activation in BR may help clarify the biochemical basis of BR. This study aimed to investigate changes in cortisol, melatonin, tryptophan (Trp), serotonin (5-hydroxytryptamine, 5-HT), KYN, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) levels in saliva samples taken from individuals with possible BR, and to examine whether there are differences in these parameters between individuals with possible sleep bruxism (SB) and possible combined bruxism (CB).

Methods: The study included 84 individuals with possible BR and 84 age-matched healthy controls. BR symptoms were assessed with a five-item questionnaire evaluating sleep- and awake-related grinding and clenching behaviors. Morning saliva samples were collected and analyzed by ELISA to determine concentrations of cortisol, melatonin, Trp, 5-HT, KYN, TNF-α, and IFN-γ. The degradation rate of Trp was evaluated using the KYN/Trp ratio (KTR). Biochemical parameters were compared between groups. Correlation analyses assessed relationships among variables, and regression analyses identified independent predictors of bruxism subtypes.

Results: Saliva cortisol, TNF-α, KYN, and KTR levels were higher, and Trp and IFN-γ levels were lower in the possible BR group than in the control group (p < 0.001 for all comparisons). Saliva cortisol, TNF-α, KYN, and KTR levels were higher (p < 0.001 for all comparisons), and melatonin levels were lower in the possible SB group than in the possible CB (p < 0.01). In the possible BR group, cortisol levels were positively correlated with KYN and KTR and negatively correlated with IFN-γ. Low Trp levels were a common independent predictor across both possible BR, while TNF-α was the only independent predictor distinguishing possible SB from possible CB.

Conclusion: Our results suggest an interaction among stress-related neuroendocrine responses, immune activation, and Trp metabolism in BR. Patients with possible SB had higher levels of cortisol, KYN, KTR, and TNF-α than those with possible CB, suggesting that SB may be more closely linked to stress and inflammation. Our results may contribute to understanding the interactions among HPA axis activity, inflammation, and Trp metabolism in BR, as well as the biochemical basis of BR type differences.