title: Efficacy of Anti-NaV1.7 Antibody on the Sensory Nervous System in a Rat Model of Lumbar Intervertebral Disc Injury.
abstract: OBJECTIVE
  The pathophysiology of discogenic low back pain is not fully understood. Tetrodotoxin-sensitive voltage-gated sodium (NaV) channels are associated with primary sensory nerve transmission, and the NaV1.7 channel has emerged as an analgesic target. Previously, we found increased NaV1.7 expression in dorsal root ganglion (DRG) neurons innervating injured discs. This study aimed to examine the effect of blocking NaV1.7 on sensory nerves after disc injury.
  
  
  METHODS
  Rat DRG neurons innervating the L5/6 disc were labeled with Fluoro-Gold (FG) neurotracer. Twenty-four rats underwent intervertebral disc puncture (puncture group) and 12 rats underwent sham surgery (non-puncture group). The injury group was divided into a saline infusion group (puncture+saline group) and a NaV1.7 inhibition group, injected with anti-NaV1.7 antibody (puncture+anti-NaV1.7 group); n=12 per group. Seven and 14 days post-surgery, L1 to L6 DRGs were harvested and immunostained for calcitonin gene-related peptide (CGRP) (an inflammatory pain marker), and the proportion of CGRP-immunoreactive (IR) DRG neurons of all FG-positive neurons was evaluated.
  
  
  RESULTS
  The ratio of CGRP-IR DRG neurons to total FG-labeled neurons in the puncture+saline group significantly increased at 7 and 14 days, compared with the non-puncture group, respectively (p<0.05). Application of anti-NaV1.7 into the disc significantly decreased the ratio of CGRP-IR DRG neurons to total FG-labeled neurons after disc puncture at 7 and 14 days (40% and 37%, respectively; p<0.05).
  
  
  CONCLUSIONS
  NaV1.7 antibody suppressed CGRP expression in disc DRG neurons. Anti-NaV1.7 antibody is a potential therapeutic target for pain control in patients with lumbar disc degeneration.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nojima
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Inage
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakuma
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Sato
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Sumihisa
authors.initials: S
authors.lastname: Orita
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Yamauchi
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yawara
authors.initials: Y
authors.lastname: Eguchi
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Ochiai
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kuniyoshi
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Aoki
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Nakamura
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyagi
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Gou
authors.initials: G
authors.lastname: Kubota
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sainoh
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Fujimoto
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shiga
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Abe
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kanamoto
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Inoue
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. sohtori@faculty.chiba-u.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Ohtori
mesh_terms: D000818:Animals; D000906:Antibodies; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism*; D007403:Intervertebral Disc / Q000187:drug effects* / Q000293:injuries*; D055959:Intervertebral Disc Degeneration / Q000378:metabolism; D017116:Low Back Pain / Q000503:physiopathology*; D008159:Lumbar Vertebrae / Q000293:injuries; D008297:Male; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010146:Pain / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013266:Stilbamidines
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D000906:Antibodies; D062556:NAV1.7 Voltage-Gated Sodium Channel; D013266:Stilbamidines; D015740:Calcitonin Gene-Related Peptide
keywords: CGRP; Low back pain; NaV1.7; intervertebral disc; rat