Asian Spine J.  2016 Aug;10(4):619-623. 10.4184/asj.2016.10.4.619.

Dose Optimization for Single Intradiscal Administration of the Tumor Necrosis Factor-α Inhibitor, Etanercept, in Rat Disc Injury Models

• Inage K
• Orita S
• Yamauchi K
• Suzuki T
• Suzuki M
• Sakuma Y
• Kubota G
• Oikawa Y
• Sainoh T
• Sato J
• Fujimoto K
• Shiga Y
• Abe K
• Kanamoto H
• Inoue M
• Kinoshita
• Takahashi
• Ohtori S

• KMID: 2349282
• DOI: http://doi.org/10.4184/asj.2016.10.4.619

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.

Keyword

Degenerative intervertebral disc; Tumor necrosis factor-alpha; Etanercept; Dose; Optimization

MeSH Terms

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
Calcitonin Gene-Related Peptide
Etanercept
Tumor Necrosis Factor-alpha