title: Involvement of trigeminal ganglionic Nav 1.7 in hyperalgesia of inflamed temporomandibular joint is dependent on ERK1/2 phosphorylation of glial cells in rats.
abstract: BACKGROUND
  Inflammation is a major cause of temporomandibular disorder-related pain. The Nav 1.7 sodium channel has a critical function in pain perceptions. However, whether and how Nav 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 Freund's adjuvant in female rats. The expression of trigeminal ganglionic Nav 1.7 and other sodium channels was examined using real-time polymerase chain reaction or Western blotting. Immunohistofluorescence with fluorescent retrograde neuronal tracer DiI was used to confirm Nav 1.7 in the trigeminal neurons innervating TMJ. The functions of trigeminal ganglionic Nav 1.7 and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation were blocked with the microinjection of the Nav 1.7 antibody or U0126 into the trigeminal ganglion. Head withdrawal threshold and food intake was measured to evaluate TMJ nociceptive responses.
  
  
  RESULTS
  TMJ inflammation significantly up-regulated Nav 1.7 mRNA and protein; however, the mRNA of Nav 1.3 was not affected and those of Nav 1.8 and Nav 1.9 were only slightly up-regulated. TMJ inflammation specifically induced Nav 1.7 in the neurons innervating TMJ. In addition, blocking the Nav 1.7 function significantly attenuated the hyperalgesia of the inflamed TMJ. Moreover, TMJ inflammation up-regulated ERK1/2 phosphorylation only in the glials; blocking ERK1/2 phosphorylation in the glials blocked Nav 1.7 up-regulation in the neurons and correspondingly attenuated the hyperalgesia of the inflamed TMJ.
  
  
  CONCLUSIONS
  Trigeminal ganglionic Nav 1.7 has an important function in the hyperalgesia of the inflamed TMJ, which is dependent on the communication with the satellite glials.
authors.affiliation: The Third Dental Center, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: R-Y
authors.initials: RY
authors.lastname: Bi
authors.forename: X-X
authors.initials: XX
authors.lastname: Kou
authors.forename: Z
authors.initials: Z
authors.lastname: Meng
authors.forename: X-D
authors.initials: XD
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Ding
authors.forename: Y-H
authors.initials: YH
authors.lastname: Gan
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006930:Hyperalgesia / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D013704:Temporomandibular Joint / Q000378:metabolism* / Q000473:pathology; D012668:Trigeminal Ganglion / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation
chemical_list: D062556:NAV1.7 Voltage-Gated Sodium Channel; C503480:Scn9a protein, rat; D048052:Mitogen-Activated Protein Kinase 3