From Nociception to Chronicity: Neurobiological Mechanisms of Orofacial Pain

Abstract

The term orofacial pain encompasses a diverse group of disorders affecting the highly innervated oral, facial, jaw, and associated tissues and constitutes one of the most frequent and disabling dental and medical complaints. It also has a different neurobiological basis from that of pain in other parts of the body due to its unique anatomical and functional organization of the trigeminal system. The present review aims to map out the continuum from acute nociception to persistent chronic pain. It starts with the peripheral transduction of noxious stimulation by trigeminal nociceptors and the molecular machinery that transduces noxious stimulation into electrical signals, such as transient receptor potential channels. These signals are then transmitted to the trigeminal brainstem sensory nuclear complex, with particular focus on the subnucleus caudalis and the phenomenon of afferent convergence that is responsible for referred pain. The review highlights peripheral and central sensitization as key amplifying mechanisms, neuroimmune and glial mechanisms that sustain these processes, and descending pathways that modulate nociceptive traffic. Special focus is placed on the transition from acute to chronic pain (chronification), maladaptive neuroplasticity, structural reorganization, and the roles of genetic, psychological, and affective factors. A key contribution of this review is the integration of peripheral, central, neuroimmune, epigenetic, and psychosocial mechanisms into a single, mechanism-based framework of orofacial pain chronification specific to the trigeminal system. This integration has not previously been assembled in this form. A mechanism-based understanding of these processes is important for making an appropriate diagnosis and for developing individualized management strategies for orofacial pain.