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

  • 1Department of Orthopedic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
  • 2Department of Orthopedic Surgery, Chiba Aoba Municipal Hospital, Chiba, Japan.
  • 3Department of Orthopedic Surgery, Kitasato University Hospital, Tokyo, Japan.
  • 4Department of Orthopedic Surgery, National Hospital Organization Chiba Medical Center, Chiba, Japan.
  • 5Department of Orthopedic Surgery, Eastern Chiba Medical Center, Chiba, Japan.
  • 6Department of Orthopedic Surgery, Chiba Children's Hospital, Chiba, Japan.
  • 7Department of Orthopedic Surgery, Sainou Hospital, Toyama, Japan.


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.
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.
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).
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.


Intervertebral discs; Back pain; Vascular endothelial growth factor

MeSH Terms

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