ERK-GluR1 phosphorylation in trigeminal spinal subnucleus caudalis neurons is involved in pain associated with dry tongue.
BACKGROUND
Dry mouth is known to cause severe pain in the intraoral structures, and many dry mouth patients have been suffering from intraoral pain. In development of an appropriate treatment, it is crucial to study the mechanisms underlying intraoral pain associated with dry mouth, yet the detailed mechanisms are not fully understood. To evaluate the mechanisms underlying pain related to dry mouth, the dry-tongue rat model was developed. Hence, the mechanical or heat nocifensive reflex, the phosphorylated extracellular signal-regulated kinase and phosphorylated GluR1-IR immunohistochemistries, and the single neuronal activity were examined in the trigeminal spinal subnucleus caudalis of dry-tongue rats.


RESULTS
The head-withdrawal reflex threshold to mechanical, but not heat, stimulation of the tongue was significantly decreased on day 7 after tongue drying. The mechanical, but not heat, responses of trigeminal spinal subnucleus caudalis nociceptive neurons were significantly enhanced in dry-tongue rats compared to sham rats on day 7. The number of phosphorylated extracellular signal-regulated kinase-immunoreactive cells was also significantly increased in the trigeminal spinal subnucleus caudalis following noxious stimulation of the tongue in dry-tongue rats compared to sham rats on day 7. The decrement of the mechanical head-withdrawal reflex threshold (HWT) was reversed during intracisternal administration of the mitogen-activated protein kinase kinase 1 inhibitor, PD98059. The trigeminal spinal subnucleus caudalis neuronal activities and the number of phosphorylated extracellular signal-regulated kinase-immunoreactive cells following noxious mechanical stimulation of dried tongue were also significantly decreased following intracisternal administration of PD98059 compared to vehicle-administrated rats. Increased number of the phosphorylated GluR1-IR cells was observed in the trigeminal spinal subnucleus caudalis of dry-tongue rats, and the number of phosphorylated GluR1-IR cells was significantly reduced in PD98059-administrated rats compared to the vehicle-administrated tongue-dry rats.


CONCLUSIONS
These findings suggest that the pERK-pGluR1 cascade is involved in central sensitization of trigeminal spinal subnucleus caudalis nociceptive neurons, thus resulting in tongue mechanical hyperalgesia associated with tongue drying.
Department of Oral Diagnostic Sciences, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
Yuka
Y
Nakaya
Department of Physiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
Yoshiyuki
Y
Tsuboi
Department of Oral Diagnostic Sciences, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
Akiko
A
Okada-Ogawa
Department of Physiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
Masamichi
M
Shinoda
Department of Physiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
Asako
A
Kubo
Department of Physiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
Jui Yen
JY
Chen
Department of Oral Diagnostic Sciences, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
Noboru
N
Noma
Department of Maxillofacial Surgery, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
Dulguun
D
Batbold
Department of Oral Diagnostic Sciences, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
Yoshiki
Y
Imamura
Department of Oral Physiology, Faculty of Dentistry, University of Toronto, Toronto, Canada.
Barry J
BJ
Sessle
Department of Physiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan iwata.kouichi@nihon-u.ac.jp.
Koichi
K
Iwata
D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D059225:Nociception / Q000187:drug effects; D010146:Pain / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects; D013997:Time Factors; D014059:Tongue / Q000473:pathology*; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects / Q000378:metabolism*; D014987:Xerostomia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology
D048049:Extracellular Signal-Regulated MAP Kinases; D005419:Flavonoids; D018091:Receptors, AMPA; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
Tongue pain; caudalis; dry mouth; medulla; phosphorylated GluR1; phosphorylated extracellular signal-regulated kinase