Department of Physiology, Medical College of Nanchang University, Jiangxi, PR China.
Brain Res Bull. 2010 Oct 30;83(5):284-91. doi: 10.1016/j.brainresbull.2010.08.002. Epub 2010 Aug 10.
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.
神经病理性疼痛的发病机制复杂。P2X₂（/）₃受体在慢性疼痛的伤害感受转导中起着关键作用。VEGF 抑制剂对缓解疼痛有效。本研究探讨了 VEGF 和 VEGF 受体-2（VEGFR2）对初级感觉神经元中 P2X₂（/）₃受体介导的神经病理性疼痛状态下疼痛传递的影响。采用慢性压迫性损伤（CCI）模型作为神经病理性疼痛模型。将 Sprague-Dawley 大鼠随机分为假手术组、CCI 组和 CCI 大鼠用抗 rVEGF 抗体治疗组。测量机械缩足阈值和热缩足潜伏期。免疫组织化学、RT-PCR 和 Western blot 分析检测 L4-6 背根神经节（DRG）中 VEGF、VEGFR2 和 P2X₂（/）₃的表达。CCI 组的机械缩足阈值和热缩足潜伏期低于假手术组和 CCI 大鼠用抗 rVEGF 抗体治疗组（p<0.05），而 L4-6 DRG 中 VEGF、VEGFR2 和 P2X₂（/）₃受体的表达CCI 组高于其他两组（p<0.05）。CCI 大鼠用抗 rVEGF 抗体治疗组的 L4-6 DRG 中 VEGF、VEGFR2 和 P2X₂（/）₃的表达低于 CCI 组（p<0.05）。结果表明，VEGF 和 VEGFR2 参与神经病理性疼痛的发病机制，VEGF 主要增强 DRG 神经元上 P2X₂（/）₃受体介导的疼痛反应。CCI 大鼠用抗 rVEGF 治疗可能通过降低 DRG 神经元上 VEGFR2 和 P2X₂（/）₃受体的表达来抑制神经病理性疼痛信号的传递，从而减轻慢性神经病理性疼痛。
