• Mol Pain · Jan 2016

    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.

    • Azumi Suzuki, Masamichi Shinoda, Kuniya Honda, Tetsuro Shirakawa, and Koichi Iwata.
    • Department of Pediatric Dentistry, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
    • Mol Pain. 2016 Jan 1; 12.

    BackgroundPain 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.ResultsHeat 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.ConclusionsThese 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.© The Author(s) 2016.

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