Efficacy of Anti-NaV1.7 Antibody on the Sensory Nervous System in a Rat Model of Lumbar Intervertebral Disc Injury.
10.3349/ymj.2016.57.3.748
- Author:
Daisuke NOJIMA
1
;
Kazuhide INAGE
;
Yoshihiro SAKUMA
;
Jun SATO
;
Sumihisa ORITA
;
Kazuyo YAMAUCHI
;
Yawara EGUCHI
;
Nobuyasu OCHIAI
;
Kazuki KUNIYOSHI
;
Yasuchika AOKI
;
Junichi NAKAMURA
;
Masayuki MIYAGI
;
Miyako SUZUKI
;
Gou KUBOTA
;
Takeshi SAINOH
;
Kazuki FUJIMOTO
;
Yasuhiro SHIGA
;
Koki ABE
;
Hirohito KANAMOTO
;
Gen INOUE
;
Kazuhisa TAKAHASHI
;
Seiji OHTORI
Author Information
1. Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. sohtori@faculty.chiba-u.jp
- Publication Type:Original Article
- Keywords:
Low back pain;
NaV1.7;
intervertebral disc;
CGRP;
rat
- MeSH:
Animals;
Antibodies;
Calcitonin Gene-Related Peptide/metabolism;
Disease Models, Animal;
Ganglia, Spinal/*metabolism;
Intervertebral Disc/*drug effects/*injuries;
Intervertebral Disc Degeneration/metabolism;
Low Back Pain/*physiopathology;
Lumbar Vertebrae/injuries;
Male;
NAV1.7 Voltage-Gated Sodium Channel/*metabolism;
Neurons/*metabolism;
Pain/metabolism;
Rats;
Rats, Sprague-Dawley;
Stilbamidines
- From:Yonsei Medical Journal
2016;57(3):748-753
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: 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. MATERIALS AND 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). CONCLUSION: 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.
