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      VEGF and its receptor-2 involved in neuropathic pain transmission mediated by P2X₂(/)₃ receptor of primary sensory neurons.

      Brain Research Bulletin

      Animals, Ganglia, Spinal, cytology, Male, Neuralgia, metabolism, Neurons, Afferent, Pain Measurement, Pain Threshold, Random Allocation, Rats, Rats, Sprague-Dawley, Receptors, Purinergic P2X2, Receptors, Purinergic P2X3, Sensory Receptor Cells, Signal Transduction, physiology, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-2

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          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. Copyright © 2010 Elsevier Inc. All rights reserved.

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