Dose Optimization for Single Intradiscal Administration of the Tumor Necrosis Factor-α Inhibitor, Etanercept, in Rat Disc Injury Models.
10.4184/asj.2016.10.4.619
- Author:
Kazuhide INAGE
1
;
Sumihisa ORITA
;
Kazuyo YAMAUCHI
;
Takane SUZUKI
;
Miyako SUZUKI
;
Yoshihiro SAKUMA
;
Go KUBOTA
;
Yasuhiro OIKAWA
;
Takeshi SAINOH
;
Jun SATO
;
Kazuki FUJIMOTO
;
Yasuhiro SHIGA
;
Koki ABE
;
Hirohito KANAMOTO
;
Masahiro INOUE
;
Hideyuki KINOSHITA
;
Kazuhisa TAKAHASHI
;
Seiji OHTORI
Author Information
1. Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. kazuhideinage@yahoo.co.jp
- Publication Type:Original Article
- Keywords:
Degenerative intervertebral disc;
Tumor necrosis factor-alpha;
Etanercept;
Dose;
Optimization
- MeSH:
Animals;
Calcitonin Gene-Related Peptide;
Diagnosis-Related Groups;
Etanercept*;
Ganglia, Spinal;
Intervertebral Disc;
Intervertebral Disc Degeneration;
Models, Animal;
Necrosis*;
Needles;
Neurons;
Rats*;
Tumor Necrosis Factor-alpha
- From:Asian Spine Journal
2016;10(4):619-623
- CountryRepublic of Korea
- Language:English
-
Abstract:
STUDY DESIGN: Experimental animal study. PURPOSE: We aimed to determine the optimal dose of a single direct injection of the tumor necrosis factor (TNF)-α inhibitor, etanercept, by using the rat model of degenerative intervertebral disc from injury. OVERVIEW OF LITERATURE: The pain-related peptide expression was suppressed in the etanercept (100 µg and 1,000 µg)-administered groups in a dose-dependent manner. METHODS: The neurotracer FluoroGold (FG) was applied to the surfaces of L4/5 discs to label their innervating dorsal root ganglion (DRG) neurons (n=50). Ten rats were included in the nonpunctured disc sham surgery control group, whereas the other 40 were included in the experimental group in which intervertebral discs were punctured with a 23-gauge needle. Saline or etanercept (10 µg, 100 µg, or 1,000 µg) was injected into the punctured discs (n=10 for each treatment). After 14 days of surgery, DRGs from L1 to L6 were harvested, sectioned, and immunostained for calcitonin gene-related peptide (CGRP). The proportion of FG-labeled CGRP-immunoreactive DRG neurons was evaluated in all the groups. RESULTS: There were no significant differences between the puncture+saline group and the puncture+10-µg etanercept group (p >0.05). However, a significant decrease in the percentage of FG and CGRP double-positive cells in FG-positive cells was observed in the etanercept (100 µg and 1,000 µg)-administered groups in a dose-dependent manner (p <0.05). CONCLUSIONS: When a low dose of the TNF-α inhibitor (10 µg of etanercept) was directly administered to the rat intervertebral disc in the rat model of degenerative intervertebral disc from injury, no suppressive effect on the pain-related peptide expression was observed. However, when a higher dose of etanercept (100 µg and 1,000 µg) was administered, the pain-related peptide expression was suppressed in a dose-dependent manner.
