Objective: To make an intensive study of the pathogenesis of orofacial pain caused by overextended opening. Methods: Observation of the histopathological changes and the immunological reactions of SP and PGE2, PGF2-alpha in the temporomandibular joint (TMJ) and masticatory muscles of the animal models of overextended opening; measure the pressure-pain thresholds in the orofacial area of 24 healthy volunteers before and after overextended opening. Results: Both TMJ and masticatory muscles suffered injury from overextended opening and there were obvious accumulations of SP and PGE2, PGE2-alpha in the injury areas; the pressure-pain thresholds in the orofacial area were decreases significantly after overextended opening, and had almost recovered 24-48 hours after overextended opening, although there were individual differences and anatomical position features in the reactions to overextended opening. Conclusions: Overextended opening can injure the TMJ and the masticatory muscles and cause an initiation into orofacial pain, endogenous algogenic substances had a hand in the course.