Increased expression of vascular endothelial growth factor protein in dorsal root ganglion exposed to nucleus pulposus on the nerve root in rats.
METHODS
An experimental rat study.


OBJECTIVE
To assess pain-related behavior and vascular endothelial growth factor (VEGF) expression induced by nucleus pulposus (NP) applied to nerve roots in rats.


BACKGROUND
Radiculopathy from disc herniation is caused by nerve compression and chemical inflammation. In experimental studies, a decrease in mechanical withdrawal threshold, blood flow, and nerve root dysfunction was reported when the NP was applied to nerve roots. However, neuron reproduction and changes in nerve root blood vessels have not been clearly understood.


METHODS
NP harvested from the tail was applied to the left L5 dorsal root ganglion (NP group; n = 77). As a control, sham-operated animals were used (n = 77). Behavioral testing with von Frey hairs was performed for 35 days. Immunoreactivity (IR) for VEGF, activating transcription factor-3, growth-associated protein-43 (GAP-43), factor VIII, and hypoxia-inducible factor-1[alpha] (HIF-1 a) were studied by immunohistochemistry. Western blot analyses of VEGF and GAP-43 were also performed.


RESULTS
The mechanical withdrawal threshold significantly decreased from 7 to 28 days in the NP group versus the sham group (P < 0.05). In the NP group, activating transcription factor-3-IR cells increased from 3 to 14 days (P < 0.05), hypoxia-inducible factor-1[alpha]-IR cells increased at 14 days (P < 0.05), and blood vessels with Factor VII-IR cells increased at 28 days (P < 0.05) compared with the sham group. The expression levels of VEGF and GAP-43 in the NP group significantly increased at 14 and 28 days (P < 0.05).


CONCLUSIONS
Neuron damage induced by NP applied to the nerve root at the early stage, and axon extension occurred from 14 days. VEGF increased at 14 and 28 days, and the numbers of blood vessels increased 28 days after surgery. The mechanical withdrawal threshold improved at 35 days. Regeneration and vascularization by VEGF might be associated with pain-related behavior.
Department of Orthopedic Surgery, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan. miyoshishinji@hotmail.com
Shinji
S
Miyoshi
Miho
M
Sekiguchi
Shin-ichi
S
Konno
Shin-ichi
S
Kikuchi
Fuminori
F
Kanaya
D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western; D004195:Disease Models, Animal; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D005727:Ganglia, Spinal / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000378:metabolism* / Q000503:physiopathology; D007405:Intervertebral Disc Displacement / Q000378:metabolism* / Q000503:physiopathology; D008159:Lumbar Vertebrae / Q000378:metabolism* / Q000503:physiopathology; D018919:Neovascularization, Physiologic; D009416:Nerve Regeneration; D017288:Pain Threshold; D051381:Rats; D017207:Rats, Sprague-Dawley; D013126:Spinal Nerve Roots / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; D019922:GAP-43 Protein; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D005169:Factor VIII