Inflammatory, oxidative, and neurotrophic profiles in monozygotic twins discordant for pain-related TMD

This study investigated the biological mechanisms underlying temporomandibular disorder (TMD) pain in monozygotic twins discordant for the condition, isolating environmental factors from genetic influence. Twenty women (ten pairs of discordant twins) underwent standardized examinations and venous plasma analysis. Inflammatory biomarkers (IL-6, IL-10), oxidative markers (MDA, SOD, catalase), matrix remodeling proteins (MMP-2, MMP-9, TIMP-1, TIMP-2), and neurotrophic factors (BDNF, β-NGF, α2M) were measured. Twins with painful TMD demonstrated greater pain severity, functional interference, and mechanical sensitivity compared to discordant controls. Significant within-pair differences were identified in IL-6, IL-6/IL-10 ratio, MDA/SOD ratio, MMP-9, TIMP-2, and BDNF levels. Pro-inflammatory and oxidative indices positively correlated with pain intensity and palpation sensitivity, while reduced BDNF associated with greater symptom burden. Principal component analysis revealed a dominant inflammatory-oxidative profile that discriminated painful twins from controls. In genetically identical individuals, painful TMD associates with selective peripheral biological alterations involving inflammation, oxidative imbalance, and extracellular matrix remodeling. These findings could demonstrate that environmental and experiential factors biologically may contribute to vulnerability to chronic orofacial pain, highlighting the importance of epigenetic mechanisms in TMD pathogenesis beyond genetic predisposition. This article identifies specific peripheral biomarker profiles distinguishing monozygotic twins with and without painful TMD, and could show that inflammation, oxidative imbalance, matrix remodeling, and reduced neurotrophic support characterize the painful phenotype. These mechanistic insights could enable clinicians to develop targeted, biologically informed therapeutic strategies and potentially predict pain vulnerability in genetically susceptible individuals.