title: Involvement of AMPA receptor GluR2 and GluR3 trafficking in trigeminal spinal subnucleus caudalis and C1/C2 neurons in acute-facial inflammatory pain.
abstract: To evaluate the involvement of trafficking of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) GluR2 and GluR3 subunits in an acute inflammatory orofacial pain, we analyzed nocifensive behavior, phosphorylated extracellular signal-regulated kinase (pERK) and Fos expression in Vi/Vc, Vc and C1/C2 in GluR2 delta7 knock-in (KI), GluR3 delta7 KI mice and wild-type mice. We also studied Vc neuronal activity to address the hypothesis that trafficking of GluR2 and GluR3 subunits plays an important role in Vi/Vc, Vc and C1/C2 neuronal activity associated with orofacial inflammation in these mice. Late nocifensive behavior was significantly depressed in GluR2 delta7 KI and GluR3 delta7 KI mice. In addition, the number of pERK-immunoreactive (IR) cells was significantly decreased bilaterally in the Vi/Vc, Vc and C1/C2 in GluR2 delta7 KI and GluR3 delta7 KI mice compared to wild-type mice at 40 min after formalin injection, and was also significantly smaller in GluR3 delta7 KI compared to GluR2 delta7 KI mice. The number of Fos protein-IR cells in the ipsilateral Vi/Vc, Vc and C1/C2 was also significantly smaller in GluR2 delta7 KI and GluR3 delta7 KI mice compared to wild-type mice 40 min after formalin injection. Nociceptive neurons functionally identified as wide dynamic range neurons in the Vc, where pERK- and Fos protein-IR cell expression was prominent, showed significantly lower spontaneous activity in GluR2 delta7 KI and GluR3 delta7 KI mice than wild-type mice following formalin injection. These findings suggest that GluR2 and GluR3 trafficking is involved in the enhancement of Vi/Vc, Vc and C1/C2 nociceptive neuronal excitabilities at 16-60 min following formalin injection, resulting in orofacial inflammatory pain.
authors.affiliation: Department of Anesthesiology, Nihon University School of Dentistry, Kandasurugadai, Chiyoda-ku, Tokyo, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Miyamoto
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tsuboi
authors.forename: Kuniya
authors.initials: K
authors.lastname: Honda
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Kogo
authors.initials: K
authors.lastname: Takamiya
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kondo
authors.forename: Masamichi
authors.initials: M
authors.lastname: Shinoda
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Sessle
authors.forename: Ayano
authors.initials: A
authors.lastname: Katagiri
authors.forename: Daiju
authors.initials: D
authors.lastname: Kita
authors.forename: Ikuko
authors.initials: I
authors.lastname: Suzuki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Oi
authors.forename: Koichi
authors.initials: K
authors.lastname: Iwata
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D059787:Acute Pain / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005157:Facial Pain / Q000378:metabolism* / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D010147:Pain Measurement; D010766:Phosphorylation / Q000187:drug effects; D018091:Receptors, AMPA / Q000378:metabolism*; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D048049:Extracellular Signal-Regulated MAP Kinases; C104722:glutamate receptor ionotropic, AMPA 2