title: Connexin 43 contributes to ectopic orofacial pain following inferior alveolar nerve injury.
abstract: BACKGROUND
  Clinically, it is well known that injury of mandibular nerve fiber induces persistent ectopic pain which can spread to a wide area of the orofacial region innervated by the uninjured trigeminal nerve branches. However, the exact mechanism of such persistent ectopic orofacial pain is not still known. The present study was undertaken to determine the role of connexin 43 in the trigeminal ganglion on mechanical hypersensitivity in rat whisker pad skin induced by inferior alveolar nerve injury. Here, we examined changes in orofacial mechanical sensitivity following inferior alveolar nerve injury. Furthermore, changes in connexin 43 expression in the trigeminal ganglion and its localization in the trigeminal ganglion were also examined. In addition, we investigated the functional significance of connexin 43 in relation to mechanical allodynia by using a selective gap junction blocker (Gap27).
  
  
  RESULTS
  Long-lasting mechanical allodynia in the whisker pad skin and the upper eyelid skin, and activation of satellite glial cells in the trigeminal ganglion, were induced after inferior alveolar nerve injury. Connexin 43 was expressed in the activated satellite glial cells encircling trigeminal ganglion neurons innervating the whisker pad skin, and the connexin 43 protein expression was significantly increased after inferior alveolar nerve injury. Administration of Gap27 in the trigeminal ganglion significantly reduced satellite glial cell activation and mechanical hypersensitivity in the whisker pad skin. Moreover, the marked activation of satellite glial cells encircling trigeminal ganglion neurons innervating the whisker pad skin following inferior alveolar nerve injury implies that the satellite glial cell activation exerts a major influence on the excitability of nociceptive trigeminal ganglion neurons.
  
  
  CONCLUSIONS
  These findings indicate that the propagation of satellite glial cell activation throughout the trigeminal ganglion via gap junctions, which are composed of connexin 43, plays a pivotal role in ectopic mechanical hypersensitivity in whisker pad skin following inferior alveolar nerve injury.
authors.affiliation: Department of Orthodontics, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan shinoda.masamichi@nihon-u.ac.jp.
authors.forename: Kaori
authors.initials: K
authors.lastname: Kaji
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Shinoda
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
authors.forename: Kuniya
authors.initials: K
authors.lastname: Honda
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
authors.forename: Syumpei
authors.initials: S
authors.lastname: Unno
authors.affiliation: Department of Orthodontics, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Shimizu
authors.affiliation: Department of Physiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Iwata
mesh_terms: D000818:Animals; D018031:Connexin 43 / Q000378:metabolism*; D017630:Connexins / Q000494:pharmacology; D005157:Facial Pain / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000150:complications / Q000473:pathology; D008297:Male; D008340:Mandibular Nerve / Q000187:drug effects / Q000473:pathology*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides; D017207:Rats, Sprague-Dawley; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D061221:Trigeminal Nerve Injuries / Q000150:complications* / Q000473:pathology
chemical_list: D018031:Connexin 43; D017630:Connexins; D005904:Glial Fibrillary Acidic Protein; D009842:Oligopeptides; C455880:gap 27 peptide
keywords: Trigeminal ganglion; connexin 43; ectopic mechanical allodynia; gap junction; inferior alveolar nerve injury; satellite glial cell