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

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.

• Authors: Kazuhide Inage, 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
• Journal: Asian spine journal (Asian Spine J) Vol. 10 Issue 4 Pg. 619-23 (Aug 2016) ISSN: 1976-1902 [Print] Korea (South)
• PMID: 27559439 (Publication Type: Journal Article)