Vascular endothelial growth factor and spinal cord injury pain.
Vascular endothelial growth factor (VEGF)-A mRNA was previously identified as one of the significantly upregulated transcripts in spinal cord injured tissue from adult rats that developed allodynia. To characterize the role of VEGF-A in the development of pain in spinal cord injury (SCI), we analyzed mechanical allodynia in SCI rats that were treated with either vehicle, VEGF-A isoform 165 (VEGF(165)), or neutralizing VEGF(165)-specific antibody. We have observed that exogenous administration of VEGF(165) increased both the number of SCI rats that develop persistent mechanical allodynia, and the level of hypersensitivity to mechanical stimuli. Our analysis identified excessive and aberrant growth of myelinated axons in dorsal horns and dorsal columns of chronically injured spinal cords as possible mechanisms for both SCI pain and VEGF(165)-induced amplification of SCI pain, suggesting that elevated endogenous VEGF(165) may have a role in the development of allodynia after SCI. However, the neutralizing VEGF(165) antibody showed no effect on allodynia or axonal sprouting after SCI. It is possible that another endogenous VEGF isoform activates the same signaling pathway as the exogenously-administered 165 isoform and contributes to SCI pain. Our transcriptional analysis revealed that endogenous VEGF(188) is likely to be the isoform involved in the development of allodynia after SCI. To the best of our knowledge, this is the first study to suggest a possible link between VEGF, nonspecific sprouting of myelinated axons, and mechanical allodynia following SCI.
Nesic
Olivera
O
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555-1072, USA. olnesic@utmb.edu
Sundberg
Laura M
LM
Herrera
Juan J
JJ
Mokkapati
Venkata U L
VU
Lee
Julieann
J
Narayana
Ponnada A
PA
D000818:Animals; D057134:Antibodies, Neutralizing; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy*; D007150:Immunohistochemistry; D008297:Male; D009043:Motor Activity; D020411:Oligonucleotide Array Sequence Analysis; D017288:Pain Threshold / Q000502:physiology; D010812:Physical Stimulation; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy*; D018709:Statistics, Nonparametric; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000627:therapeutic use
D057134:Antibodies, Neutralizing; D042461:Vascular Endothelial Growth Factor A