Fig. 6

Schematic results of the current study. (1) Hsp70 is expressed in the pulpal tissue following tooth pulp exposure. (2) Hsp70 is axonally transported from the inflamed tooth pulp of the lower first molar to the trigeminal ganglion. (3) Transported Hsp70 is released into the intercellular space in the trigeminal ganglion. (4) Hsp70 binds to the toll-like receptor 4 of trigeminal ganglion neurons innervating the tongue and promotes IL-1RI expression. (5) Simultaneously, the accumulated macrophages following tooth pulp inflammation generate and release IL-1β in the extracellular space in the trigeminal ganglion. Larger amounts of IL-1β bind to the larger number of IL-1RI of trigeminal ganglion neurons innervating the tongue. (6) The IL-1β/IL-1RI signaling facilitates TRPV1 expression. (7) Enhanced expression of TRPV1 on the tongue-innervating trigeminal ganglion neurons promotes neuronal excitability and results in mechanical and heat hypersensitivity of the tongue