Association Between Central Sensitization, Dopaminergic Biomarkers, and Clinical Parameters in Women With Chronic Painful Temporomandibular Disorder

• Grant number: 25/11277-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Laís Valencise Magri
• Grantee: Lívia Prado Remédio
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Introduction: Chronic painful temporomandibular disorder (TMD) is a multifactorial condition that significantly impairs the quality of life of women in their productive years. Growing evidence suggests that central sensitization mechanisms and alterations in neurotransmitter systems, such as the dopaminergic pathway, play a relevant role in pain chronification. Genetic polymorphisms related to dopamine, as well as plasma levels of this neurotransmitter, may influence pain perception and clinical presentation in affected individuals; however, this relationship remains poorly understood in populations with TMD. Objective: To investigate the association between central sensitization symptoms, plasma dopamine levels, dopaminergic genetic variants, and clinical pain manifestations in women with chronic painful TMD. Materials and Methods: This is an observational, analytical, and cross-sectional study involving a sample of 60 women aged between 18 and 50 years, diagnosed with chronic painful TMD according to the Diagnostic Criteria for TMD (DC/TMD). Pain classification will follow the International Classification of Orofacial Pain (ICOP). Participants will complete the Central Sensitization Inventory (CSI) and validated psychometric instruments. Blood samples will be collected for plasma dopamine quantification using HPLC-MS/MS and genotyping of polymorphisms. Genotyping of the COMT (rs4680), DRD4 (VNTR), and DAT1 (VNTR) polymorphisms will be conducted via PCR. Statistical analyses will include correlation tests, group comparisons, and multivariate regression models, with a significance level set at p < 0.05. Expected Outcomes: It is expected that women with chronic painful TMD and central sensitization symptoms will exhibit lower plasma dopamine levels compared to those without central sensitization. Additionally, it is anticipated that dopaminergic gene variants-particularly COMT (rs4680), DRD4 (VNTR), and DAT1 (VNTR) polymorphisms-will be associated with higher pain intensity, greater functional impact, and more pronounced psychosocial symptoms. Finally, both dopamine biomarkers and central sensitization scores are expected to serve as significant predictors of clinical TMD manifestations, contributing to the understanding of neurobiological mechanisms involved in orofacial pain chronification.