Genetic risk factors for the development of chronic orofacial pain and masticatory muscle dysfunction in temporomandibular joint pain-dysfunction syndrome

Temporomandibular disorder (TMD) pain represents a multifactorial musculoskeletal condition, ranking as the second most common chronic pain condition after chronic low back pain. Contemporary research confirms its biopsychosocial nature, determined by genetic predisposition leading to central sensitization, and a wide spectrum of interacting psychosocial and physiological factors that shape the chronic orofacial pain syndrome. This article analyzes the role of genetic factors in the development and chronification of TMD pain. Key genetic markers identified include variations in the COMT gene (val158met, rs4680), which influence catechol-O-methyltransferase activity and regulate dopaminergic/adrenergic neurotransmission. Low-activity COMT alleles (met/met) correlate with heightened pain sensitivity, increased risk of pain chronification, and elevated anxiety. Polymorphisms in the ADRB2 (rs1042713) and HTR1A (rs6295) genes are associated with myofascial pain and allodynia. Variations in ADRB2 influence pain sensitivity linked to symptoms of somatization, depression, and anxiety — phenotypic characteristics commonly observed in individuals with generalized chronic pain and TMD. Studies, including the large-scale OPPERA project, demonstrate that genetic variations determine not only pain susceptibility but also treatment response. Specifically, carriers of minor alleles in COMT and OPRM1 exhibit poorer treatment outcomes, highlighting the need for a personalized approach in diagnosis and therapy. These findings underscore the complexity of the genetic architecture underlying Temporomandibular Disorder pain syndrome, necessitating further research and enhanced international collaboration to expand patient cohorts. Integrating genetic data into clinical practice could improve prediction of pain chronification, optimize treatment strategies, and develop preventive measures, thereby reducing the socioeconomic burden of the disease.