VEGF and its receptor-2 involved in neuropathic pain transmission mediated by P2X₂(/)₃ receptor of primary sensory neurons.
The pathogenesis of neuropathic pain is complex. P2X₂(/)₃ receptor plays a crucial role in nociception transduction of chronic pain. VEGF inhibitors are effective for pain relief. The present study investigated the effects of VEGF and VEGF receptor-2 (VEGFR2) on the pain transmission in neuropathic pain states that mediated by P2X₂(/)₃ receptor in primary sensory neurons. Chronic constriction injury (CCI) model was used as neuropathic pain model. Sprague-Dawley rats had been randomly divided into sham group, CCI group and CCI rats treated with anti-rVEGF antibody group. Mechanical withdrawal threshold and thermal withdrawal latency were measured. Expressions of VEGF, VEGFR2 and P2X₂(/)₃ in L4-6 dorsal root ganglia (DRG) were detected by immunohistochemistry, RT-PCR and western blot analysis. The mechanical withdrawal threshold and thermal withdrawal latency in CCI group were lower than those in sham group and CCI rats treated with anti-rVEGF antibody group (p<0.05), while VEGF, VEGFR2 and P2X₂(/)₃ receptors' expressions of L4-6 DRG in CCI group were higher than those in the other two groups (p<0.05). The expressions of VEGF, VEGFR2 and P2X₂(/)₃ in L4-6 DRG of CCI rats treated with anti-rVEGF antibody group were decreased compared with those in CCI group (p<0.05). The results show that VEGF and VEGFR2 are involved in the pathogenesis of neuropathic pain and VEGF primarily potentiates pain responses mediated by P2X₂(/)₃ receptor on DRG neurons. Anti-rVEGF treatment in CCI rats may alleviate chronic neuropathic pain by decreasing the expressions of VEGFR2 and P2X₂(/)₃ receptors on DRG neurons to inhibit the transmission of neuropathic pain signaling.
Lin
Jiari
J
Department of Physiology, Medical College of Nanchang University, Jiangxi, PR China.
Li
Guilin
G
Den
Xiaorong
X
Xu
Changshui
C
Liu
Shuangmei
S
Gao
Yun
Y
Liu
Han
H
Zhang
Jun
J
Li
Xin
X
Liang
Shangdong
S
D000818:Animals; D005727:Ganglia, Spinal / Q000166:cytology; D008297:Male; D009437:Neuralgia / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism*; D010147:Pain Measurement; D017288:Pain Threshold; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D058476:Receptors, Purinergic P2X2 / Q000378:metabolism*; D058477:Receptors, Purinergic P2X3 / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2