Targeting orofacial pain: From pathophysiological mechanisms to Traditional Chinese Medicine approaches

Orofacial pain is a heterogeneous group of painful conditions affecting the facial and oral regions that can substantially impair quality of life. In some patients, stimulus-evoked pain manifestations such as allodynia further aggravate the disease burden. Current drugs, including carbamazepine and pregabalin, offer only partial relief and are limited by adverse effects, underscoring the need for alternative therapeutic strategies. Traditional Chinese Medicine (TCM), characterized by holistic and multi-targeted actions, shows therapeutic promise. This review summarizes recent advances in peripheral and central mechanisms of orofacial pain, emphasizing ion channel dysregulation, central sensitization, neuroinflammation, and gut-brain axis modulation. We further evaluate TCM-derived phytochemicals, including resveratrol, curcumin, and α-bisabolol. These compounds act by modulating neuroimmune pathways, suppressing glial activation, restoring synaptic plasticity, and rebalancing gut microbiota. Finally, we highlight challenges-such as standardization, biomarker-guided diagnostics, and the lack of large-scale clinical trials-and propose future directions. By linking traditional insights with contemporary neuroscience, this review aims to provide a mechanistic framework for effective, personalized, and sustainable therapies.