Pathophysiology of orofacial neuropathic pain: A narrative review on the multi-level cascade of neuro-glial plasticity
J Oral Biosci. 2026 Jun 2;68(4):100795. doi: 10.1016/j.job.2026.100795. Online ahead of print.
ABSTRACT
BACKGROUND: Orofacial neuropathic pain has a complex pathophysiology beyond simple neuronal hyperexcitability. In this review, recent evidence is synthesized on the multi-level cascade of neuro-glial plasticity-from the trigeminal ganglion (TG) to higher brain centers-and its role in pain chronicity and affective distress is examined.
HIGHLIGHT: Peripheral nerve injury activates satellite glial cells in the TG and microglia/astrocytes in the trigeminal sensory nuclear complex, driving central sensitization and circuit reorganization. These changes extend to affective circuits and the descending pain modulatory system, where astrocytes in the rostral ventromedial medulla facilitate pro-nociceptive states. Emerging perspectives also highlight the potential role of meningeal lymphatic dysfunction in prolonging neuroinflammation.
CONCLUSION: Orofacial neuropathic pain is conceptualized as a "multi-level gliopathy". A more detailed understanding of these stage-specific neuro-glial interactions and homeostatic clearance systems will provide a novel framework for the development of mechanism-based therapeutic strategies.
PMID:42229053 | DOI:10.1016/j.job.2026.100795