title: p38 phosphorylation in medullary microglia mediates ectopic orofacial inflammatory pain in rats.
abstract: BACKGROUND
  Orofacial inflammatory pain is likely to accompany referred pain in uninflamed orofacial structures. The ectopic pain precludes precise diagnosis and makes treatment problematic, because the underlying mechanism is not well understood. Using the established ectopic orofacial pain model induced by complete Freund's adjuvant (CFA) injection into trapezius muscle, we analyzed the possible role of p38 phosphorylation in activated microglia in ectopic orofacial pain.
  
  
  RESULTS
  Mechanical allodynia in the lateral facial skin was induced following trapezius muscle inflammation, which accompanied microglial activation with p38 phosphorylation and hyperexcitability of wide dynamic range (WDR) neurons in the trigeminal spinal subnucleus caudalis (Vc). Intra-cisterna successive administration of a p38 mitogen-activated protein kinase selective inhibitor, SB203580, suppressed microglial activation and its phosphorylation of p38. Moreover, SB203580 administration completely suppressed mechanical allodynia in the lateral facial skin and enhanced WDR neuronal excitability in Vc. Microglial interleukin-1β over-expression in Vc was induced by trapezius muscle inflammation, which was significantly suppressed by SB203580 administration.
  
  
  CONCLUSIONS
  These findings indicate that microglia, activated via p38 phosphorylation, play a pivotal role in WDR neuronal hyperexcitability, which accounts for the mechanical hypersensitivity in the lateral facial skin associated with trapezius muscle inflammation.
authors.affiliation: Department of Oral Physiology, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan. kiyomoto49@dent.showa-u.ac.jp.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kiyomoto
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo, 101-8310, 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, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo, 101-8310, Japan. honda.kuniya@nihon-u.ac.jp.
authors.forename: Kuniya
authors.initials: K
authors.lastname: Honda
authors.affiliation: Department of Oral Diagnostic Sciences, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo, 101-8310, Japan. yukchun1126@gmail.com.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Nakaya
authors.affiliation: Department of Oral Diagnostic Sciences, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo, 101-8310, Japan. deko12026@g.nihon-u.ac.jp.
authors.forename: Ko
authors.initials: K
authors.lastname: Dezawa
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo, 101-8310, Japan. katagiri.ayano@nihon-u.ac.jp.
authors.forename: Ayano
authors.initials: A
authors.lastname: Katagiri
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo, 101-8310, Japan. kamakura314@i.softbank.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kamakura
authors.affiliation: Department of Oral Physiology, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan. inouet@dent.showa-u.ac.jp.
authors.forename: Tomio
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo, 101-8310, Japan. iwata.kouichi@nihon-u.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Iwata
mesh_terms: D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D005157:Facial Pain / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D005620:Freund's Adjuvant; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D007267:Injections; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D017628:Microglia / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D053583:Interleukin-1beta; D011725:Pyridines; D005620:Freund's Adjuvant; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580