Duloxetine attenuates pain in association with downregulation of platelet serotonin transporter in patients with burning mouth syndrome and atypical odontalgia

Abstract

Objective:The aim of this study was evaluation of the association between severity of pain and expression of total or ubiquitinated serotonin transporter (SERT) protein in patients with burning mouth syndrome and atypical odontalgia (BMS/AO), who were treated by duloxetine.Methods: Patients with BMS/AO were assessed for severity of pain using the visual analog scale (VAS), and expression of total and ubiquitinated SERT protein in platelets before (baseline) and 12 weeks after duloxetine-treatment. Results:The expression of total and ubiquitinated SERT protein at baseline in all patients (n = 33) were higher and lower, respectively, compared to those in healthy controls. 12 weeks after duloxetine-treatment, there was no difference in the total SERT protein levels between patients (n = 21) and healthy controls. In the 16 patients who could be measured, mean VAS scores and total SERT protein levels were significantly decreased after the treatment, compared to those at baseline. There was tendency for a positive correlation between total SERT protein levels and VAS scores in these patients. Conclusions:Our findings indicate that duloxetine relieves pain in association with downregulation of platelet SERT expression in patients with BMS/AO.

Duloxetine improves chronic orofacial pain and comorbid depressive symptoms in association with reduction of serotonin transporter protein through upregulation of ubiquitinated serotonin transporter protein

“…In conclusion, this showed increased expression of SERT protein and decreased expression of its ubiquitinated protein in platelets of untreated COP patients, regardless of comorbid depressive symptoms. These findings support the results of previous studies, 53 and reveal that total and ubiquitinated SERT protein levels could be potential biomarkers for the diagnosis of COP patients such as BMS and PIFP regardless of comorbid depressive symptoms. In addition, 12 weeks of DLX treatment suppressed the increased expression of SERT protein and improved pain and depressive symptoms in COP-D patients, suggesting that ubiquitinated SERT protein levels may be associated with the severity of depressive symptoms.…”

“…All COP patients (diagnosed with BMS and PIFP) 53 were longly recruited from the liaison outpatient clinic of Aichi Gakuin University Dental Hospital between April 2014 and December 2022 because of collecting participants suitable for stratified analyses. Forty-nine COP patients (9 men and 40 women) were treated with DLX for 12 weeks from the initial dose of 20 mg once daily, and after 2 weeks or more, the dose was gradually increased to a maximum of 40 mg once daily as previously described.…”

“…Forty-nine COP patients (9 men and 40 women) were treated with DLX for 12 weeks from the initial dose of 20 mg once daily, and after 2 weeks or more, the dose was gradually increased to a maximum of 40 mg once daily as previously described. 35,45,51,53 Exclusion criteria were as follows: history of psychiatric disorders, dementia, or serious physical disease; previous use of DLX; and use of any psychotropic agent within 2 weeks of participation in this study. Healthy controls without any episodes of orofacial pain or psychiatric disorder and without any medications affecting the expression of SERT (ex.…”

“…44,66 The effectiveness of DLX for COP has been demonstrated, and it is used one of the promising treatment options. 33,35,43,53,55 Furthermore, genetic polymorphisms in SERT, the target molecule of DLX, have been reported to be associated with pain threshold, 67 sensitivity, 32,57 and the development of depression. Alterations in the gene and protein expressions and function of SERT affect the severity of pain as well as depressive symptoms.…”

Burning Mouth Syndrome And Its Relation To Disorders Of Orofacial Pain

“…It is generally believed that pain in the oral cavity results from a lack of pain inhibition in the central region of the brain in response to changes in taste, particularly a bitter taste that is caused by hormones. There is evidence to suggest that the application of a topical anaesthetic rinse makes the burning sensation caused by BMS worse (Nakamura et al, 2022). This research also explains why supertasters, who are disproportionately female are at the greatest risk of experiencing phantom oral sensations after taste impairment.…”