Duloxetine significantly relieved chronic nonorganic orofacial pain. Its pain-relieving effect appeared from 2 weeks of treatment. Furthermore, the pain-relieving effects of duloxetine similarly appeared regardless of the presence or absence of baseline depressive symptoms.

Previous reports have shown that during chronic inflammation, the tryptophan (TRP)-kynurenine (KYN) pathway plays a pivotal role in the onset of depression. The aim of this study was to investigate the characteristics of the serum TRP-KYN pathway metabolite profile in high-risk subjects of major depressive disorder (HRMDD) defined by depression scores. The concentrations of TRP-KYN pathway metabolites {TRP, KYN, 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), kynurenic acid (KYNA) and anthranilic acid (AA)} were assessed in serum from HRMDD, chronic pain disorder patients and healthy controls. In serum from HRMDD, elevated levels of AA and decreased levels of TRP were observed, but the levels of other metabolites were not changed. Furthermore, the change in the AA 2nd / AA 1st ratio in subjects who progressed from a healthy state to a depressive state was correlated with an increase in the CES-D score. The level of IL-1 receptor antagonist (IL-1RA) was negatively correlated with that of AA. Interestingly, we confirmed AA as a possible biomarker for depression-related symptoms, since the metabolite profiles in the chronic pain disorder group and chronic unpredictable mild stress model mice were similar to those in the HRMDD. These results suggest that AA may be an effective marker for HRMDD. More than 300 million people suffered from major depressive disorder (MDD) in 2017, and the number is increasing year by year 1. Several theories of MDD onset have been proposed 2. The monoamine hypothesis, the chronic inflammation hypothesis, and the abnormalities in the hypothalamus-pituitary-adrenal (HPA) system hypothesis are the predominant hypotheses regarding the pathogenesis of MDD 3. Among these hypotheses, the chronic inflammation hypothesis is closely associated with the kynurenine (KYN) pathway 4. The KYN pathway is one of several tryptophan (TRP) metabolism pathways, and it is the main pathway involved in TRP metabolism 5,6. Inflammatory cytokines such as IFN-γ induce the expression of indoleamine 2,3-dioxygenase (IDO1), which is a

Objective Burning mouth syndrome (BMS) and atypical odontalgia (AO) are examples of somatic symptom disorders with predominant pain around the orofacial region. Neuroinflammation is thought to play a role in the mechanisms, but few studies have been conducted. We aimed to better understand the role of neuroinflammation in the pathophysiology and treatment of BMS/AO. Methods Plasma levels of 28 neuroinflammation‐related molecules were determined in 44 controls and 48 BMS/AO patients both pretreatment and 12‐week post‐treatment with duloxetine. Results Baseline plasma levels of interleukin (IL)‐1β (p < .0001), IL‐1 receptor antagonist (p < .001), IL‐6 (p < .0001), macrophage inflammatory protein‐1β (p < .0001), and platelet‐derived growth factor‐bb (.04) were significantly higher in patients than in controls. Plasma levels of granulocyte macrophage colony stimulating factor were significantly higher in patients than in controls (p < .001) and decreased with treatment (.009). Plasma levels of eotaxin, monocyte chemoattractant protein‐1, and vascular endothelial growth factor decreased significantly with treatment (p < .001, .022, and .029, respectively). Conclusions Inflammatory mechanisms may be involved in the pathophysiology and/or treatment response of somatic symptom disorders with predominant pain around the orofacial region.

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Duloxetine significantly relieved pain in patients with chronic nonorganic pain in the orofacial region. However, no relationship was observed between its pain-relieving effects and plasma concentrations.