Asian Spine Journal (Aug 2017)

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

  • Jun Sato,
  • Kazuhide Inage,
  • Masayuki Miyagi,
  • Yoshihiro Sakuma,
  • Kazuyo Yamauchi,
  • Masao Koda,
  • Takeo Furuya,
  • Junichi Nakamura,
  • Miyako Suzuki,
  • Go Kubota,
  • Yasuhiro Oikawa,
  • Takeshi Sainoh,
  • Kazuki Fujimoto,
  • Yasuhiro Shiga,
  • Koki Abe,
  • Hirohito Kanamoto,
  • Masahiro Inoue,
  • Hideyuki Kinoshita,
  • Masaki Norimoto,
  • Tomotaka Umimura,
  • Kazuhisa Takahashi,
  • Seiji Ohtori,
  • Sumihisa Orita

DOI
https://doi.org/10.4184/asj.2017.11.4.556
Journal volume & issue
Vol. 11, no. 4
pp. 556 – 561

Abstract

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Study DesignAn experimental animal study.PurposeTo 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 LiteratureIncreased 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.MethodsThrough 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.ResultsCompared 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).ConclusionsDecreasing 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.

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