Involvement of trigeminal ganglionic N a v 1.7 in hyperalgesia of inflamed temporomandibular joint is dependent on ERK 1/2 phosphorylation of glial cells in rats

Background Inflammation is a major cause of temporomandibular disorder‐related pain. The N a v 1.7 sodium channel has a critical function in pain perceptions. However, whether and how N a v 1.7 in the trigeminal ganglion is involved in temporomandibular joint ( TMJ ) inflammatory pain remains to be examined. Methods TMJ inflammation was induced by complete F reund's adjuvant in female rats. The expression of trigeminal ganglionic N a v 1.7 and other sodium channels was examined using real‐time polymerase chain reaction or W estern blotting. Immunohistofluorescence with fluorescent retrograde neuronal tracer DiI was used to confirm N a v 1.7 in the trigeminal neurons innervating TMJ . The functions of trigeminal ganglionic N a v 1.7 and extracellular signal‐regulated kinase 1/2 ( ERK 1/2) phosphorylation were blocked with the microinjection of the N a v 1.7 antibody or U 0126 into the trigeminal ganglion. Head withdrawal threshold and food intake was measured to evaluate TMJ nociceptive responses. Results TMJ inflammation significantly up‐regulated N a v 1.7 mRNA and protein; however, the mRNA of N a v 1.3 was not affected and those of N a v 1.8 and N a v 1.9 were only slightly up‐regulated. TMJ inflammation specifically induced N a v 1.7 in the neurons innervating TMJ . In addition, blocking the N a v 1.7 function significantly attenuated the hyperalgesia of the inflamed TMJ . Moreover, TMJ inflammation up‐regulated ERK 1/2 phosphorylation only in the glials; blocking ERK 1/2 phosphorylation in the glials blocked N a v 1.7 up‐regulation in the neurons and correspondingly attenuated the hyperalgesia of the inflamed TMJ . Conclusions Trigeminal ganglionic N a v 1.7 has an important function in the hyperalgesia of the inflamed TMJ , which is dependent on the communication with the satellite glials.