The Pathophysiological Mechanisms of Glia in Animal Models of Chronic Orofacial Pain: A Systematic Review

Background/Objectives: Chronic orofacial pain represents a heterogeneous group of disorders affecting the trigeminal system and remains difficult to treat due to its complex pathophysiology, which involves glial cells in the development and maintenance of persistent pain states. This systematic review aimed to synthesize evidence from animal studies investigating the pathophysiological role of glial cells in chronic orofacial pain. Methods: After registering on PROSPERO, a systematic search of the literature, based on PRISMA guidelines, was conducted to identify experimental animal studies evaluating glial involvement in orofacial pain models. After screening and eligibility assessment, 10 studies met the inclusion criteria. Data regarding experimental models, glial populations investigated, and pain-related behavioral outcomes were extracted and qualitatively synthesized. Results: Activation of satellite glial cells, microglia, and astrocytes was consistently associated with increased neuroinflammatory signaling and enhanced neuronal excitability within trigeminal pathways, demonstrating that both peripheral and central nervous tissues were involved. Several studies reported that pharmacological modulation of glial activity may reduce pain-related behaviors. Conclusions: Glial cells are key modulators of chronic orofacial pain through neuroimmune interactions that contribute to peripheral and central sensitization. Although these findings highlight promising therapeutic targets, further translational research is required to clarify their relevance for human pain conditions.