title: Regulation of transient receptor potential vanilloid 1 expression in trigeminal ganglion neurons via methyl-CpG binding protein 2 signaling contributes tongue heat sensitivity and inflammatory hyperalgesia in mice.
abstract: BACKGROUND
  Pain hypoalgesia has been reported in Rett syndrome patients, a severe neurodevelopmental disorder which can be attributed to mutations in the methyl-CpG binding protein 2 (MeCP2). Here, we examined the role of MeCP2 signaling in tongue heat sensitivity in the normal and inflamed state using Mecp2 heterozygous (Mecp2(+/-)) mice.
  
  
  RESULTS
  Heat hypoalgesia of the tongue occurred in Mecp2(+/-) mice and submucosal injection of complete Freund's adjuvant into the tongue produced a long-lasting heat hyperalgesia at the inflamed site in wild-type mice but not in Mecp2(+/-) mice. Transient receptor potential vanilloid 1 was expressed in a large number of MeCP2-immunoreactive trigeminal ganglion neurons innervating the tongue in both wild-type and Mecp2(+/-) mice (70.9% in wild type; 72.1% in Mecp2(+/-)). The number of transient receptor potential vanilloid 1-immunoreactive trigeminal ganglion neurons innervating the tongue was smaller in Mecp2(+/-) mice relative to wild-type mice (30.5% in wild type; 20.2% in Mecp2(+/-)). Following complete Freund's adjuvant injection, the number of transient receptor potential vanilloid 1- and MeCP2-immunoreactive trigeminal ganglion neurons innervating the tongue, as well as MeCP2 protein expression in trigeminal ganglion, was significantly increased in wild-type mice but not in Mecp2(+/-) mice. Additionally, tongue heat hyperalgesia following complete Freund's adjuvant injection was completely suppressed by the administration of SB366791, a transient receptor potential vanilloid 1 antagonist, in the tongue.
  
  
  CONCLUSIONS
  These findings indicate that tongue heat sensitivity and hypersensitivity are dependent on the expression of transient receptor potential vanilloid 1 which is regulated via MeCP2 signaling in trigeminal ganglion neurons innervating the tongue.
authors.affiliation: Department of Pediatric Dentistry, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
authors.forename: Azumi
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan shinoda.masamichi@nihon-u.ac.jp.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Shinoda
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
authors.forename: Kuniya
authors.initials: K
authors.lastname: Honda
authors.affiliation: Department of Pediatric Dentistry, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Shirakawa
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Iwata
mesh_terms: D000818:Animals; D000075369:Anoctamin-1; D018118:Chloride Channels / Q000378:metabolism; D005260:Female; D005620:Freund's Adjuvant; D006358:Hot Temperature; D006930:Hyperalgesia / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D017288:Pain Threshold; D012018:Reflex; D015398:Signal Transduction; D050053:TRPM Cation Channels / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism*; D013997:Time Factors; D014059:Tongue / Q000294:innervation / Q000473:pathology*; D012668:Trigeminal Ganglion / Q000378:metabolism* / Q000473:pathology
chemical_list: C531181:ANO1 protein, mouse; D000075369:Anoctamin-1; D018118:Chloride Channels; D051783:Methyl-CpG-Binding Protein 2; D050053:TRPM Cation Channels; C533868:TRPM3 protein, mouse; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D005620:Freund's Adjuvant
keywords: Rett syndrome; Trigeminal ganglion; tongue inflammation; transient receptor potential vanilloid 1