Asian Spine J.  2017 Aug;11(4):556-561. 10.4184/asj.2017.11.4.556.

Inhibiting Vascular Endothelial Growth Factor in Injured Intervertebral Discs Attenuates Pain-Related Neuropeptide Expression in Dorsal Root Ganglia in Rats

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

• KMID: 2387660
• DOI: http://doi.org/10.4184/asj.2017.11.4.556

Abstract

STUDY DESIGN: An experimental animal study. PURPOSE: To evaluate effects of anti-vascular endothelial growth factor (VEGF) on the content and distribution of the calcitonin gene-related peptide (CGRP) in the dorsal ganglia in a rat model. OVERVIEW OF LITERATURE: Increased expression of VEGF in degenerative disc disease increases the levels of inflammatory cytokines and nerve ingrowth into the damaged discs. In animal models, increased levels of VEGF can persist for up to 2 weeks after an injury.
METHODS
Through abdominal surgery, the dorsal root ganglia (DRG) innervating L5/L6 intervertebral disc were labeled (FluoroGold neurotracer) in 24, 8-week old Sprague Dawley rats. The rats were randomly allocated to three groups of eight rats each. The anti-VEGF group underwent L5/6 intervertebral disc puncture using a 26-gauge needle, intradiscal injection of 33.3 µg of the pegaptanib sodium, a VEGF165 aptamer. The control-puncture group underwent disc puncture and intradiscal injection of 10 µL saline solution, and the sham-surgery group underwent labeling but no disc puncture. Two rats in each group were sacrificed on postoperative days 1, 7, 14, and 28 after surgery. L1-L6 DRGs were harvested, sectioned, and immunostained to detect the content and distribution of CGRP.
RESULTS
Compared with the control, the percentage of CGRP-positive cells was lower in the anti-VEGF group (p<0.05; 40.6% and 58.1% on postoperative day 1, 44.3% and 55.4% on day 7, and 42.4% and 59.3% on day 14). The percentage was higher in the control group compared with that of the sham group (p<0.05; sham group, 34.1%, 40.7%, and 33.7% on postoperative days 1, 7, and 14, respectively).
CONCLUSIONS
Decreasing CGRP-positive cells using anti-VEGF therapy provides fundamental evidence for a possible therapeutic role of anti-VEGF in patients with discogenic lower back pain.

Keyword

Intervertebral discs; Back pain; Vascular endothelial growth factor

MeSH Terms

Animals
Back Pain
Calcitonin Gene-Related Peptide
Cytokines
Diagnosis-Related Groups
Endothelial Growth Factors
Ganglia
Ganglia, Spinal*
Humans
Intervertebral Disc*
Low Back Pain
Models, Animal
Needles
Neuropeptides*
Punctures
Rats*
Rats, Sprague-Dawley
Sodium
Sodium Chloride
Spinal Nerve Roots*
Vascular Endothelial Growth Factor A*
Calcitonin Gene-Related Peptide
Cytokines
Endothelial Growth Factors
Neuropeptides
Sodium
Sodium Chloride
Vascular Endothelial Growth Factor A