Orofacial musculoskeletal pain: An evidence-based bio-psycho-social matrix model

•Chronic orofacial pain is a highly prevalent and clinically relevant condition.•Social, psychological and biological factors may all facilitate and modulate the orofacial pain process.•Pain, negative emotions, insomnia and stress-related cortical activity promote a feedforward neural network.•Cortical, subcortical and cerebellar areas disrupt the homeostatic state which may result in pain chronicity.•An interdisciplinary therapeutic strategy based on a biopsychosocial model is essential for effective pain management. Pain is a multidimensional experience comprising sensory-discriminative, affective-motivational, and cognitive-evaluative dimensions. Clinical and research findings have demonstrated a complex interplay between social burdens, individual coping strategies, mood states, psychological disorders, sleep disturbances, masticatory muscle tone, and orofacial musculoskeletal pain. Accordingly, current classification systems for orofacial pain require psychosocial assessments to be an integral part of the multidimensional diagnostic process. Here, we review evidence on how psychosocial and biological factors may generate and perpetuate musculoskeletal orofacial pain. Specifically, we discuss studies investigating a putative causal relationship between stress, bruxism, and pain in the masticatory system. We present findings that attribute brain structures various roles in modulating pain perception and pain-related behavior. We also examine studies investigating how the nervous and immune system on cellular and molecular levels may account for orofacial nociceptive signaling. Furthermore, we review evidence pointing towards associations between orofacial musculoskeletal pain and neuroendocrine imbalances, sleep disturbances, and alterations of the circadian timing system. We conclude with several proposals that may help to alleviate orofacial pain in the future.