Neural Mechanisms and Brain Alterations in Orofacial Pain: A Narrative Review of Human Neuroimaging

Abstract

Orofacial pain is a complex and multifactorial condition that affects quality of life and presents important diagnostic and therapeutic challenges. Advances in neuroimaging techniques have enabled the investigation of nervous system alterations associated with pain perception and modulation. This review synthesizes current evidence on structural, functional, and neurochemical brain alterations identified through magnetic resonance imaging (MRI) in individuals with acute and chronic orofacial pain conditions. A comprehensive literature search of PubMed, Web of Science, and Scopus identified MRI studies (structural, diffusion, functional) in adults with temporomandibular disorders, trigeminal neuralgia, persistent dentoalveolar pain, or experimental pain. The main results demonstrated alterations along peripheral trigeminal pathways, brainstem nuclei, and central pain processing networks. Additionally, it was also possible to verify altered gray- and white matter integrity, causing disrupted connectivity within large-scale networks related to pain modulation and cognitive processing. While acute pain reflects transient activation of these pathways, chronic and neuropathic conditions can involve persistent structural and functional reorganization across sensory, affective, and cognitive networks. These findings support the involvement of distributed neural mechanisms and neuroplastic changes in many chronic orofacial pain conditions, while emphasizing that peripheral, central, psychosocial, and contextual factors may contribute to varying degrees across disorders and individuals. Multimodal MRI may provide a basis for future diagnostic, prognostic, and treatment response biomarkers, although most advanced MRI-derived markers remain investigational.