title: Differential Changes in Neuronal Excitability in the Spinal Dorsal Horn After Spinal Nerve Ligation in Rats.
abstract: Previous studies demonstrated that peripheral nerve injury induced excessive neuronal response and glial activation in the spinal cord dorsal horn, and such change has been proposed to reflect the development and maintenance of neuropathic pain states. The aim of this study was to examine neuronal excitability and glial activation in the spinal dorsal horn after peripheral nerve injury. We examined noxious heat stimulation-induced c-Fos protein-like immunoreactivity (Fos-LI) neuron profiles in fourth-to-sixth lumbar (L4-L6) level spinal dorsal horn neurons after fifth lumbar spinal nerve ligation (L5 SNL). Immunofluorescence labeling of OX-42 and GFAP was also performed in histological sections of the spinal cord. A significant increase in the number of Fos-LI neuron profiles in the spinal dorsal horn at the L4 level was found at 3 days after SNL, but returned to a level similar to that in sham-operated controls by 14 days after injury. As expected, a decrease in the number of Fos-LI neuron profiles in the spinal dorsal horn at the L5 level was found at 3 days after SNL. However, these profiles had reappeared in large numbers by 14 and 21 days after injury. Immunofluorescence labeling of OX-42 and GFAP indicated sequential activation of microglia and astrocytes in the spinal dorsal horn. We conclude that nerve injury causes differential changes in neuronal excitability in the spinal dorsal horn, which may coincide with glial activation. These changes may play a substantial role in the pathogenesis of neuropathic pain after peripheral nerve injury.
authors.affiliation: Department of Oral Function and Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan. ryujit@md.okayama-u.ac.jp.|Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School, Okayama, 700-8525, Japan. ryujit@md.okayama-u.ac.jp.
authors.forename: Ryuji
authors.identifier: http://orcid.org/0000-0003-0448-5044
authors.initials: R
authors.lastname: Terayama
authors.affiliation: Department of Oral Function and Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan.|Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8525, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Oral Function and Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan.|Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8525, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kishimoto
authors.affiliation: Department of Oral Function and Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan.|Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8525, Japan.
authors.forename: Mitsuyasu
authors.initials: M
authors.lastname: Tabata
authors.affiliation: Department of Oral Function and Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan.|Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School, Okayama, 700-8525, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Maruhama
authors.affiliation: Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8525, Japan.|Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School, Okayama, 700-8525, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Iida
authors.affiliation: Department of Oral Function and Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan.|Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School, Okayama, 700-8525, Japan.
authors.forename: Tomosada
authors.initials: T
authors.lastname: Sugimoto
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology; D008026:Ligation / Q000379:methods; D008297:Male; D017628:Microglia / Q000473:pathology; D009437:Neuralgia / Q000503:physiopathology; D059348:Peripheral Nerve Injuries / Q000378:metabolism / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D066148:Spinal Cord Dorsal Horn / Q000473:pathology*; D013127:Spinal Nerves / Q000378:metabolism / Q000473:pathology
chemical_list: D016760:Proto-Oncogene Proteins c-fos
keywords: Astrocyte; C-Fos; Microglia; Nerve injury; Spinal dorsal horn