Involvement of peripheral artemin signaling in tongue pain: possible mechanism in burning mouth syndrome.
Burning mouth syndrome is characterized by altered sensory qualities, namely tongue pain hypersensitivity. We found that the mRNA expression of Artemin (Artn) in the tongue mucosa of patients with burning mouth syndrome was significantly higher than that of control subjects, and we developed a mouse model of burning mouth syndrome by application of 2,4,6-trinitrobenzene sulfonic acid (TNBS) diluted with 50% ethanol to the dorsum of the tongue. TNBS treatment to the tongue induced persistent, week-long, noninflammatory tongue pain and a significant increase in Artn expression in the tongue mucosa and marked tongue heat hyperalgesia. Following TNBS treatment, the successive administration of the transient receptor potential vanilloid 1 (TRPV1) antagonist SB366791 or neutralizing anti-Artn antibody completely inhibited the heat hyperalgesia. The number of glial cell line-derived neurotrophic factor family receptor α3 (GFRα3)-positive and TRPV1-positive trigeminal ganglion (TG) neurons innervating the tongue significantly increased following TNBS treatment and was significantly reduced by successive administration of neutralizing anti-Artn antibody. The capsaicin-induced current in TG neurons innervating the tongue was enhanced following TNBS treatment and was inhibited by local administration of neutralizing anti-Artn antibody to the tongue. These results suggest that the overexpression of Artn in the TNBS-treated tongue increases the membrane excitability of TG neurons innervating the tongue by increasing TRPV1 sensitivity, which causes heat hyperalgesia. This model may be useful for the study of tongue pain hypersensitivity associated with burning mouth syndrome.
Department of Physiology, Nihon University School of Dentistry, Tokyo, Japan Laboratory of Food and Physiological Sciences, Department of Food and Life Sciences, School of Life and Environmental Sciences, Azabu University, Sagamihara, Japan Department of Complete Denture Prosthodontics, Nihon University School of Dentistry, Tokyo, Japan Division of Oral Diagnosis, Tohoku University Graduate School of Dentistry, Sendai, Japan Tohoku Fukushi University, Sendai, Japan.
Masamichi
M
Shinoda
Mamoru
M
Takeda
Kuniya
K
Honda
Mitsuru
M
Maruno
Ayano
A
Katagiri
Shizuko
S
Satoh-Kuriwada
Noriaki
N
Shoji
Masahiro
M
Tsuchiya
Koichi
K
Iwata
D000368:Aged; D000369:Aged, 80 and over; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D015153:Blotting, Western; D002054:Burning Mouth Syndrome / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D002934:Cinnamates / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000378:metabolism; D005926:Glossalgia / Q000139:chemically induced / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D014059:Tongue / Q000187:drug effects / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000378:metabolism*; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
C490886:ARTN protein, human; D000813:Anilides; D057134:Antibodies, Neutralizing; C116599:Artn protein, mouse; D002934:Cinnamates; C494994:Gfra3 protein, mouse; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D014302:Trinitrobenzenesulfonic Acid